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3.
  • Larsson, Max, et al. (författare)
  • Quantitative analysis of immunogold labeling indicates low levels and non-vesicular localization of L-aspartate in rat primary afferent terminals.
  • 2001
  • Ingår i: Journal of Comparative Neurology. - : John Wiley & Sons. - 0021-9967 .- 1096-9861. ; 430:2, s. 147-159
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of L-aspartate as an excitatory neurotransmitter in primary afferent synapses in the spinal cord dorsal horn is disputed. To further investigate this issue, we examined the presence of aspartate-like immunoreactivity in primary afferent nerve terminals and other tissue components of the dorsal horn. We also examined the relationship between aspartate and glutamate immunogold labeling density and the density of synaptic vesicles in primary afferent terminals and presumed inhibitory terminals forming symmetric synapses. Weak aspartate immunosignals, similar to or lower than those displayed by presumed inhibitory terminals, were detected in both C-fiber primary afferent terminals in lamina II (dense sinusoid axon terminals, identified by morphological criteria) and in A-fiber primary afferent terminals in laminae III-IV (identified with anterograde transport of choleragenoid-horseradish peroxidase conjugate). The aspartate immunogold signal in primary afferent terminals was only about one-fourth of that in deep dorsal horn neuronal cell bodies. Further, whereas significant positive correlations were evident between synaptic vesicle density and glutamate immunogold labeling density in both A- and C-fiber primary afferent terminals, none of the examined terminal populations displayed a significant correlation between synaptic vesicle density and aspartate immunogold labeling density. Thus, our results indicate relatively low levels and a non-vesicular localization of aspartate in primary afferent terminals. It is therefore suggested that aspartate, rather than being a primary afferent neurotransmitter, serves a role in the intermediary metabolism in primary afferent terminals.
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4.
  • Novikova, Liudmila N, et al. (författare)
  • BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats
  • 2000
  • Ingår i: Journal of Comparative Neurology. - : Wiley-Liss, Inc.. - 0021-9967 .- 1096-9861. ; 428:4, s. 671-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have previously been shown to support survival and axonal regeneration in various types of neurons. Also, synergistic neuroprotective effects of these neurotrophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons of Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neurons had been lost, and the remaining cells exhibited marked atrophy. Microglial activity was significantly increased in CN of the operated side. Intrathecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell survival and a reduction in cell atrophy, but did not reduce microglial activity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffective. Furthermore, when a combination of BDNF and NT-3 was administered, the neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection obtained by a combination of neurotrophic factors may be less than that of a single neurotrophin.
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5.
  • Fundin, Bengt T., et al. (författare)
  • A comprehensive immunofluorescence and lectin binding analysis of intervibrissal fur innervation in the mystacial pad of the rat
  • 1997
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 385:2, s. 185-206
  • Tidskriftsartikel (refereegranskat)abstract
    • The innervation of the intervibrissal fur in the mystacial pad of the rat and mouse wasexamined by immunofluorescence with a wide variety of antibodies for neuronal relatedstructural proteins, enzymes, and peptides as well as for lectin binding histofluorescence with Griffonia simplicifolia (GSA). Anti-protein gene product 9.5 (PGP) immunofluorescencelabeled all sets of axons and endings. The innervation in the upper dermis and epidermis wasdistributed through a four tiered dermal plexus. From deep to superficial, the second tier wasthe source of all apparent myelinated mechanorceptors, the third tier of nearly all thepeptidergic and GSA binding innervation, and the fourth tier of nonpeptidergic GSA negativeinnervation (peptide-/GSA-). Three types of mechanoreceptors—Merkel, transverse lanceolate,and longitudinal lanceolate endings—innervated guard hair follicles. All had similarlabeling characteristics for 160 kDa and 200 kDa neurofilament subunits, peripherin,carbonic anhydrase, synaptophysin, and S100. Palisades of longitudinal lanceolate endingswere part of piloneural complexes along circumferentially oriented sets of transverselanceolate endings, peptidergic free nerve endings (FNEs), and peptide-/GSA- FNEs. Thelongitudinal lanceolate endings were the only mechanoreceptors in the mystacial pad that haddetectable calcitonin gene-related peptide. The epidermis contained four types of unmyelinatedendings: simple free nerve endings (FNEs), penicillate endings, cluster endings and bushendings. Only the simple FNEs were clearly peptidergic. Virtually all others were peptide-/GSA-. Each bush ending was actually an intermingled cluster of endings formed by severalunmyelinated axons and occasionally anAd axon. In contrast to the other unmyelinated innervationto the epidermis, bush endings labeled with an antibody against the Schwann cell protein S100. Thenecks and mouths of follicles, as well as superficial vasculature, were innervated by a mixture of unmyelinated peptidergic and/or GSA labeled sensory and sympathetic axons. Small presumptivesweat glands were innervated by three sets of peptidergic axons of which one was immunoreactivefor somatostatin. Potential functions of the various sets of innervation are discussed.
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6.
  • Hallbeck, Martin, 1970-, et al. (författare)
  • Distribution of preprovasopressin mRNA in the rat central nervous system
  • 1999
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 411:2, s. 181-200
  • Tidskriftsartikel (refereegranskat)abstract
    • Vasopressin released in the central nervous system has been shown to be involved both in homeostatic mechanisms (e.g., water balance, thermoregulation, cardiovascular regulation, metabolism, and antinociception) and in higher brain functions (e.g., social recognition and communication, and learning and memory). Many nuclear groups have been proposed to synthesize vasopressin, but available data are conflicting. We have used a sensitive in situ hybridization technique to identify the distribution of the neurons that may be the origin of the vasopressin in the central nervous system of the male Sprague-Dawley rat. Vasopressin mRNA-expressing neurons were most abundant in the hypothalamus (e.g., the paraventricular, supraoptic, and suprachiasmatic nuclei) but were also seen in the medial amygdaloid nucleus, the bed nucleus of stria terminalis, and the nucleus of the horizontal diagonal band. Previously unreported vasopressinergic neurons were seen in the entorhinal and piriform cortices, the ventral lateral portion of the parabrachial nucleus, the pedunculopontine nucleus, and the rostral part of the ventral periaqueductal gray matter and the adjacent portion of the mesencephalic reticular nucleus. Vasopressin mRNA expression suggestive of neuronal labeling was seen in the pyramidal layer of the CA1–3 fields and the dentate gyrus of the hippocampus. In addition, vasopressin mRNA expression, probably representing axonal mRNA, was detected over the hypothalamopituitary tract. No or insignificant preprovasopressin mRNA expression was present in the cerebellum, locus coeruleus, subcoeruleus, or the spinal cord. These findings provide novel information on the distribution of vasopressin neurons that are important for our understanding of how vasopressin acts in the brain.
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7.
  • Hallbeck, Martin, 1970-, et al. (författare)
  • Spinal cord-projecting vasopressinergic neurons in the rat paraventricular hypothalamus
  • 1999
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 411:2, s. 201-211
  • Tidskriftsartikel (refereegranskat)abstract
    • The paraventricular hypothalamic nucleus (PVH) is a key structure for the maintenance of homeostasis. Homeostatic regulation includes modulation of signaling in the spinal cord. This may be exerted by neurons in the PVH with spinal projections. However, the PVH is not a homogeneous structure, but consists of anatomically and functionally distinct subdivisions. In this study, we have analyzed the distribution of spinal cord-projecting PVH neurons that express vasopressin, an important neuropeptide in autonomic regulation. Vasopressinergic neurons were identified with a radiolabeled riboprobe complementary to vasopressin mRNA combined with immunohistochemical labeling of retrogradely transported cholera toxin subunit b in spinally projecting neurons. More than 40% of the spinally projecting neurons in the PVH of naive Sprague-Dawley rats were found to express vasopressin mRNA. The lateral parvocellular subdivision and the ventral part of the medial parvocellular subdivision contained the densest distribution of spinal cord-projecting vasopressin mRNA-expressing neurons. The magnocellular subdivisions displayed large numbers of vasopressin mRNA-expressing neurons, but very few of those projected to the spinal cord. The dorsal parvocellular subdivision contained a large number of spinally projecting neurons, but very few of those expressed vasopressin mRNA. These findings show that the PVH gives rise to a major vasopressinergic projection to the spinal cord and that the spinal cord-projecting vasopressinergic neurons are parceled into anatomically distinct cell groups. This provides an anatomical basis for a selective activation of functionally different groups in the PVH as part of a behaviorally adaptive response, including modulation of autonomic activity and pain processing at the spinal level.
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8.
  • Hallböök, Finn, et al. (författare)
  • Expression of neurotrophins and trk receptors in the avian retina
  • 1996
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 364:4, s. 664-676
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the RNase protection assay, we have found that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are expressed in the avian retina during development. The expression peaks around embryonic days 12-15, with decreasing levels at later stages of development. Abundant levels of NGF and BDNF but low levels of NT-3 mRNA were found in the adult retina. We also found that light/darkness regulated the levels of NGF and BDNF mRNAs but not the levels of NT-3 mRNA in the 5-day-old chicken retina. It was demonstrated that NGF and BDNF mRNA levels were up-regulated by light exposure. The cellular localization of mRNA expression for the neurotrophins and neurotrophin receptors TrkA, TrkB, and TrkC in the retina was studied using in situ hybridization. The patterns of NGF and trkA mRNA expression were very similar and were localized to the external part of the inner nuclear layer on the border with the outer plexiform layer and corresponded to the localization of horizontal cells. NT-3 labeling was also found over the external part of the inner nuclear layer, whereas trkC mRNA was found over all layers in the retina. BDNF labeling was found over all layers in the retina, whereas TrkB labeling was intense over cells in the ganglion cell layer, which is in agreement with the response of ganglion cells to BDNF stimulation. Functional neurotrophin receptors were suggested by the response of retinal explants to neurotrophin stimulation. These data indicate that the neurotrophins play local roles in the retina that involve interactions between specific neuronal populations, which were identified by the localization of the Trk receptor expression. The data also suggest that NGF and BDNF expression is regulated by normal neuron usage in the retina.
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9.
  • Karlsson, Miriam, et al. (författare)
  • Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells during chicken retinal development
  • 1998
  • Ingår i: J. Comp. Neurol.. ; 400:3, s. 408-416
  • Tidskriftsartikel (refereegranskat)abstract
    • Nerve growth factor is known to stimulate neurite outgrowth and support neuronal survival during embryonic development. We have studied the expression of the nerve growth factor receptor, TrkA, at both mRNA and protein levels during the course of chicken retinal development. Furthermore, we have compared the expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late embryonic retina. Using in situ hybridization and immunohistochemistry, we found cells expressing TrkA in both the internal and the external part of the inner nuclear layer, corresponding to amacrine and horizontal cells, respectively. The TrkA-expressing amacrine cell has a unistratified dendritic arborization in the second sublamina of the inner plexiform layer, and may represent the stellate amacrine cell described by Cajal. The horizontal cells, possessing arciform dendrite processes in the outer plexiform layer, showed strong TrkA immunoreactivity in both dendrites and cell bodies. During the course of retinal development, the TrkA-expressing amacrine cells decreased in number, whereas the TrkA-expressing horizontal cells persisted. Because nerve growth factor was expressed where the horizontal cells, but not where the amacrine cells were located, these findings raise the question of whether nerve growth factor could locally support the survival of TrkA-expressing interneurons during retinal development.
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10.
  • Nässel, Dick R, et al. (författare)
  • Proline-specific dipeptidyl peptidase activity in the cockroach brain and intestine : Partial characterization, distribution, and inactivation of tachykinin-related peptides
  • 2000
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 418:1, s. 81-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Proline-specific dipeptidyl peptidase (DPP TV) is an established enzyme known to degrade neuropeptides and peptide hormones in vertebrate tissues. DPP TV cleaves peptides at the Pro(2) residue. Because several neuropeptides of the cockroach Leucophaea maderae, such as LemTRP-1 (APSGFLGVRamide), are potential substrates for this peptidase, we investigated the occurrence of proline-specific DPP activity in cockroach tissues. Partly purified DPP activity was characterized from the brain and midgut of L. maderae by using Gly-Pro-4-nitroanilide as a substrate. The highest activity was obtained from the membrane fraction of intestine; about 10 times less activity (per milligram protein) was obtained from brain membranes. A smaller amount of soluble DPP activity could also be identified in both tissues. Gel chromatography of the solubilized intestinal DPP activity revealed a molecular mass of about 75 kDa. The enzyme had a pH optimum of 8.5. Diprotin A (Ile-Pro-Ile) was an efficient competitive inhibitor of the cockroach DPP, whereas other known DPP inhibitors were found to be less potent. When incubated with human and cockroach DPP IV, the cleavage products of LemTRP-1 were AP and SGFLGVRamide (des-AP-LemTRP-1) as determined by mass spectrometry of high-performance liquid chromatography (HPLC)-purified peptide fragments. The AP fragment was biologically inactive and the des-AP fragment had a drastically reduced myostimulatory activity on the hindgut of L. maderae. The blowfly TRP callitachykinin-I (CavTK-I; APTAFYGVRamide) was cleaved in two steps to des-AP-CavTK-I and desAPTA-CavTK-I, showing that cockroach DPP does not only liberate Xaa-Pro, but also Xaa-Ala dipeptides. The fragment desAPTA-CavTK-I was completely inactive on the cockroach hindgut. To compare, LemTRP-3 and CavTK-II, which lack a Pro(2), were not cleaved by DPP IV. Enzyme histochemistry for DPP IV was performed on cryostat sections of brain and intestine with Gly-Pro-4-methoxy-2-naphthylamide as the substrate and Fast Blue B as the chromogen. Strong histochemical labeling was seen in specific neuropils of the brain such as the calyces of the mushroom bodies, the antennal glomeruli, and the central body. Also, the inner lining of the midgut (the peritrophic membrane) and the malpighian tubules were strongly labeled by reaction product. In both the brain and intestine, the enzyme-histochemical reaction was inhibited by diprotin A.
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11.
  • Rice, Frank L, et al. (författare)
  • A comprehensive immunofluorescence and lectin binding analysis of vibrissal follicle sinus complex innervation in the mystacial pad of the rat
  • 1997
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 385:2, s. 149-184
  • Tidskriftsartikel (refereegranskat)abstract
    • The innervation of the vibrissal follicle sinus complexes (FSCs) in the mystacial pad of the rat was examined by lectin binding histofluorescence with the B subunit of Griffonia simplicifolia (GSA) and by immunofluorescence with a wide variety of antibodies for neuronal related structural proteins, enzymes, and peptides. Only anti-protein gene product 9.5 labeled all sets of innervation. Several types of mechanoreceptors were distributed to specific different targets by medium to large caliber myelinated axons. All were positive for 200 kDa neurofilament subunit, peripherin, and carbonic anhydrase. Their endings expressed synaptophysin. Labeling for the 160 kDa neurofilament subunit, calbindin, and parvalbumin varied. Anti-Schwann cell protein S100 was completely co-extensive with the axons, terminal arbors, and endings of the mechanoreceptor afferents including Merkel innervation. At least 15 different sets of unmyelinated innervation were evident based upon distribution and labeling characteristics. They consisted of four basic types: 1) peptidergic; 2) GSA binding; 3) peptidergic and GSA binding; and 4) nonpeptidergic and GSA negative (peptide-/GSA-). Previous studies had not revealed that several major sets of unmyelinated innervation were peptide-/GSA-. The unmyelinated innervation had detectable peripherin but not 160 kDa or 200 kDa neurofilament subunits. GSA-positive axons uniquely lacked anti-S100 immunoreactivity. The dense circumferentially oriented unmyelinated innervation of the inner conical body contained major sets of peptide-/GSA- and GSA innervation as well as a smaller peptidergic GSA component. A small contingent of sympathetic and possibly parasympathetic innervation was affiliated with microvasculature in the FSCs. This study confirms and refutes some previous hypotheses about biochemical and morphological relationships between peripheral innervation and sensory ganglion cells.
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12.
  • von Euler, Mia, 1967-, et al. (författare)
  • Quantitative study of neurofilament-positive fiber length in rat spinal cord lesions using isotropic virtual planes
  • 1998
  • Ingår i: Journal of Comparative Neurology. - Philadelphia : John Wiley & Sons. - 0021-9967 .- 1096-9861. ; 400:4, s. 441-448
  • Tidskriftsartikel (refereegranskat)abstract
    • Spontaneous reocurrence of neurofilament (NF)-positive fibers has been described after spinal cord lesions in rats. However, previously introduced methods to evaluate the lesion and the regenerative fiber outgrowth suffer from several biases, why a new concept of quantitative, morphological analysis after spinal cord injury is needed. Length quantification of the putatively spontaneously regenerating fibers has been difficult until recently, when two length estimators based on sampling with isotropic virtual planes within thick physical sections were introduced. The applicability of these techniques to estimate the total length of NF-positive fibers was evaluated in photochemically induced ischemic lesions of thoracic spinal cords in young rats 6 weeks postlesion. Fiber length was found to be the most consistent measure with a mean of 3.71 m (coefficient of variation, CV = 0.16) in the 0.90 mm3 (CV = 0.26) large lesions. Whether or not the NF-positive fibers observed inside the lesion represent spontaneously regenerating axons needs to be confirmed in longitudinal, functional, and ultrastructural studies.
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13.
  • Adden, Andrea, et al. (författare)
  • The brain of a nocturnal migratory insect, the Australian Bogong moth
  • 2020
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 528:11, s. 1942-1963
  • Tidskriftsartikel (refereegranskat)abstract
    • Every year, millions of Australian Bogong moths (Agrotis infusa) complete an astonishing journey: In Spring, they migrate over 1,000 km from their breeding grounds to the alpine regions of the Snowy Mountains, where they endure the hot summer in the cool climate of alpine caves. In autumn, the moths return to their breeding grounds, where they mate, lay eggs and die. These moths can use visual cues in combination with the geomagnetic field to guide their flight, but how these cues are processed and integrated into the brain to drive migratory behavior is unknown. To generate an access point for functional studies, we provide a detailed description of the Bogong moth's brain. Based on immunohistochemical stainings against synapsin and serotonin (5HT), we describe the overall layout as well as the fine structure of all major neuropils, including the regions that have previously been implicated in compass-based navigation. The resulting average brain atlas consists of 3D reconstructions of 25 separate neuropils, comprising the most detailed account of a moth brain to date. Our results show that the Bogong moth brain follows the typical lepidopteran ground pattern, with no major specializations that can be attributed to their spectacular migratory lifestyle. These findings suggest that migratory behavior does not require widespread modifications of brain structure, but might be achievable via small adjustments of neural circuitry in key brain areas. Locating these subtle changes will be a challenging task for the future, for which our study provides an essential anatomical framework.
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16.
  • Beetz, M Jerome, et al. (författare)
  • Topographic organization and possible function of the posterior optic tubercles in the brain of the desert locust Schistocerca gregaria
  • 2015
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 523:11, s. 1589-1607
  • Tidskriftsartikel (refereegranskat)abstract
    • Migrating desert locusts, Schistocerca gregaria, are able to use the skylight polarization pattern for navigation. They detect polarized light with a specialized dorsal rim area in their compound eye. After multistage processing, polarization signals are transferred to the central complex, a midline-spanning brain area involved in locomotor control. Polarization-sensitive tangential neurons (TB-neurons) of the protocerebral bridge, a part of the central complex, give rise to a topographic arrangement of preferred polarization angles in the bridge, suggesting that the central complex acts as an internal sky compass. TB-neurons connect the protocerebral bridge with two adjacent brain areas, the posterior optic tubercles. To analyze the polarotopic organization of the central complex further, we investigated the number and morphologies of TB-neurons and the presence and colocalization of three neuroactive substances in these neurons. Triple immunostaining with antisera against Diploptera punctata allatostatin (Dip-AST), Manduca sexta allatotropin (Mas-AT), and serotonin (5HT) raised in the same host species revealed three spatially distinct TB-neuron clusters, each consisting of 10 neurons per hemisphere: cluster 1 and 3 showed Dip-AST/5HT immunostaining, whereas cluster 2 showed Dip-AST/Mas-AT immunostaining. Five subtypes of TB-neuron could be distinguished based on ramification patterns. Corresponding to ramification domains in the protocerebral bridge, the neurons invaded distinct but overlapping layers within the posterior optic tubercle. Similarly, neurons interconnecting the tubercles of the two hemispheres also targeted distinct layers of these neuropils. From these data we propose a neuronal circuit that may be suited to stabilize the internal sky compass in the central complex of the locust
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17.
  • Beggs, J, et al. (författare)
  • Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque
  • 2003
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 459:4, s. 334-354
  • Tidskriftsartikel (refereegranskat)abstract
    • We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 ╡m, mean width = 1.29 ╡m) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 ╡m). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.
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18.
  • Beramendi, Ana, et al. (författare)
  • Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging
  • 2007
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 501:4, s. 498-508
  • Tidskriftsartikel (refereegranskat)abstract
    • The neuromuscular junction (NMJ) of Drosophila melanogaster has been established as a productive model for the study of synaptogenesis, synaptic plasticity, vesicle recycling, and other synaptic functions in embryos and larvae. It also has potential for the study of long-term plasticity during adult life and degenerative processes associated with aging. Here we provide a detailed description of the morphology and ultrastructure of the NMJ on abdominal dorsal longitudinal muscles throughout adult life from eclosion to senescence. In contrast to the case in the larva, the predominant type of terminals in these muscles in the adult fly consists of only two or three branches with tightly packed synaptic boutons. We observed qualitative and quantitative changes as mean bouton size increased gradually during adulthood, and the largest boutons were present in the old fly. The length of nerve branches first increased and thereafter decreased gradually during most of adult life. Branch diameter also decreased progressively, but branch number did not change. The subsynaptic reticulum became progressively thinner, and “naked” boutons were found in old flies. Ultrastructural traits gave indications of an age-associated increment in autophagy, larger synaptic vesicles, and impaired endocytosis. We propose that NMJ aging in the fly correlates with impaired endocytosis and membrane dynamics. This view finds a functional correlate in flies carrying a temperature-sensitive mutation in shibire that reversible blocks endocytosis; age significantly reduces the time required for complete paralysis and increases the time of recovery, thus confirming the age-dependent alteration in vesicle dynamics.
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20.
  • Berglöf, Elisabet, et al. (författare)
  • Beneficial effects of antioxidant-enriched diet for tyrosine hydroxylase-positive neurons in ventral mesencephalic tissue in oculo grafts
  • 2009
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 515:1, s. 72-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Supplementation of antioxidants to the diet has been proved to be beneficial in aging and after brain injury. Furthermore, it has been postulated that the locus coeruleus promotes survival of dopamine neurons. Thus, this study was performed to elucidate the effects of a blueberry-enriched diet on fetal ventral mesencephalic tissue in the presence or absence of locus coeruleus utilizing the in oculo grafting method. Sprague-Dawley rats were given control diet or diet supplemented with 2% blueberries, and solid tissue pieces of fetal locus coeruleus and ventral mesencephalon were implanted as single and co-grafts. The results revealed that the presence of locus coeruleus tissue or the addition of blueberries enhanced the survival of ventral mesencephalic tyrosine hydroxylase (TH)-positive neurons, whereas no additive effects were observed for the two treatments. The density of TH-positive nerve fibers in ventral mesencephalic tissue was significantly elevated when it was attached to the locus coeruleus or by blueberry treatment, whereas the innervation of dopamine-beta-hydroxylase-positive nerve fibers was not altered. The presence of locus coeruleus tissue or bluberry supplementation reduced the number of Iba-1-positive microglia in the ventral mesencephalic portion of single and co-grafts, respectively, whereas almost no OX6 immunoreactivity was found. Furthermore, neither the attachment of ventral mesencephalic tissue nor the addition of blueberries improved the survival of TH-positive neurons in the locus coerulean grafts. To conclude, locus coeruleus and blueberries are beneficial for the survival of fetal ventral mesencephalic tissue, findings that could be useful when grafting tissue in Parkinson's disease.
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22.
  • Bras, H., et al. (författare)
  • Demonstration of initial axon collaterals of cells of origin of the ventral spinocerebellar tract in the cat
  • 1988
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 273, s. 584-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurones of origin of the ventral spinocerebellar tract were stained with intracellularly applied horseradish peroxidase to investigate whether they give off any initial axon collaterals. The neurones were located in the fourth and fifth lumbar segments and were identified by their antidromic activation following stimulation in the contralateral superior cerebellar peduncle. Nine of the 23 neurones with well‐stained axons were found to give off axon collaterals soon after the axons crossed the midline. The collaterals entered the contralateral ventral horn and branched within lamina VII and the dorsal part of lamina VIII. Collaterals were found arising only from neurones located in the middle of lamina VII and from axons which took a mediorostral direction. In all of these neurones excitatory postsynaptic potentials were evoked from group Ia afferents of at least some nerves, in addition to such potentials from Ib or unidentified group I afferents, and inhibitory postsynaptic potentials were evoked from group I and II afferents. The area of terminal branching of the collaterals suggests that they may supply contralateral ventral spinocerebellar neurones with information from muscles and/or mediate crossed reflexes from group I afferents. Copyright © 1988 Alan R. Liss, Inc.
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23.
  • Bras, H., et al. (författare)
  • Morphology of midlumbar interneurones relaying information from group II muscle afferents in the cat spinal cord
  • 1989
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 290, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • The morphology of midlumbar interneurones with peripheral input from group II muscle afferents was analysed after intracellular injection of horseradish peroxidase (HRP). Twenty‐three interneurones were stained intrasomatically and five others intra‐axonally. The majority (10 of 13) of interneurones located in lamina VII (intermediate zone and ventral horn interneurones) were found to project ipsilaterally. They had medium‐sized somata and dendrites projecting radially over a distance of more than 1 mm. All of these neurones had axons that projected caudally within the ventral part of the lateral funiculus or in the lateral part of the ventral funiculus, although four had in addition an ascending secondary axonal branch. Numerous axon collaterals were given off from these axons, both before and after they left the grey matter. The collaterals arborized within laminae VII, VIII, and IX, where they covered the area of several motor nuclei. Intra‐axonal labelling of five neurones with similar input and axon trajectories revealed several axon collaterals given off between the cell body and the terminal projection areas in L7 or S1 segments. Only three of the labelled interneurones located in lamina VII and displaying the same kind of input had axons with different destinations; their axons crossed to the opposite side of the spinal cord and ascended within the contralateral ventral funiculus. These were large neurones with extensive dendritic trees, which had fairly thick axons with initial axon collaterals that branched primarily ipsilaterally (within laminae V‐VIII). Interneurones located in lamina V and in the bordering parts of laminae IV and VI (dorsal horn interneurones; n = 10) constituted a very nonhomogenous population. They projected either ipsilaterally or contralaterally and had either ascending or descending axons running in either the lateral or ventral funiculi. Generally, dorsal horn interneurones had cell bodies smaller than those of intermediate zone and ventral horn interneurones, and their dendrites extended less extensively and less uniformly around the soma. Their initial axon collaterals branched primarily in the dorsal horn, or in lamina VII, but not in or close to the motor nuclei. Our results support the conclusions of previous physiological studies that the intermediate zone and ventral horn midlumbar interneurones with group II input and that project to motor nuclei have collateral actions on other interneurones in the L4‐L6 segments, and that dorsal horn interneurones do not project to motoneurones, but have as their targets other interneurones or ascending cells. On the other hand, we have not found any projections of L4 interneurones with input from either group I or group I1 muscle afferents, to Clarke's column, in contrast to the projections of interneurones in reflex pathways from tendon organs from more caudal segments. Copyright © 1989 Alan R. Liss, Inc.
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24.
  • Broms, Jonas, et al. (författare)
  • Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.
  • 2015
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 523:3, s. 359-380
  • Tidskriftsartikel (refereegranskat)abstract
    • The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, thus anatomically and functionally ideally positioned to regulate emotional, motivational and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G coupled-protein receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and Translating Ribosome Affinity Purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis we found that GPR151 expressing axons and terminals overlap with cholinergic, substance P-ergic and glutamatergic markers. Virtually identical expression pattern was observed in rat, mouse and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc.
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25.
  • Broms, Jonas, et al. (författare)
  • Monosynaptic retrograde tracing of neurons expressing the G-protein coupled receptor Gpr151 in the mouse brain
  • 2017
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 525:15, s. 3227-3250
  • Tidskriftsartikel (refereegranskat)abstract
    • GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. The habenula has been implicated in a range of different functions including behavioral flexibility, decision making, inhibitory control, and pain processing, which makes it a promising target for treating psychiatric and neurological disease. This study aimed to further characterize neurons expressing the Gpr151 gene, by tracing the afferent connectivity of this diencephalic cell population. Using pseudotyped rabies virus in a transgenic Gpr151-Cre mouse line, monosynaptic afferents of habenular and thalamic Gpr151-expressing neuronal populations could be visualized. The habenular and thalamic Gpr151 systems displayed both shared and distinct connectivity patterns. The habenular neurons primarily received input from basal forebrain structures, the bed nucleus of stria terminalis, the lateral preoptic area, the entopeduncular nucleus, and the lateral hypothalamic area. The Gpr151-expressing neurons in the paraventricular nucleus of the thalamus was primarily contacted by medial hypothalamic areas as well as the zona incerta and projected to specific forebrain areas such as the prelimbic cortex and the accumbens nucleus. Gpr151 mRNA was also detected at low levels in the lateral posterior thalamic nucleus which received input from areas associated with visual processing, including the superior colliculus, zona incerta, and the visual and retrosplenial cortices. Knowledge about the connectivity of Gpr151-expressing neurons will facilitate the interpretation of future functional studies of this receptor.
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26.
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27.
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28.
  • Bräutigam, Lars, et al. (författare)
  • Localized Expression of Urocortin Genes in the Developing Zebrafish rain
  • 2010
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 518:15, s. 2978-2995
  • Tidskriftsartikel (refereegranskat)abstract
    • The corticotropin-releasing hormone (CRH) family consists of four aralogous genes, CRH and urocortins (UCNs) 1, 2, and 3. In a previous tudy, we analyzed CRH in the teleost model organism zebrafish and its ranscript distribution in the embryonic brain. Here, we describe ull-length cDNAs encoding urotensin 1 (UTS1), the teleost UCN1 rtholog, and UCN3 of zebrafish. Major expression sites of uts1 in adult ebrafish are the caudal neurosecretory system and brain. By using T-PCR analysis, we show that uts1 mRNA is also present in ovary, aternally contributed to the embryo, and expressed throughout embryonic evelopment. Expression of ucn3 mRNA was detected in a range of adult issues and during developmental stages from 24 hours post fertilization nward. Analysis of spatial transcript distributions by whole-mount in itu hybridization revealed limited forebrain expression of uts1 and cn3 during early development. Small numbers of uts1-synthesizing eurons were found in subpallium, hypothalamus, and posterior iencephalon, whereas ucn3-positive cells were restricted to elencephalon and retina. The brainstem was the main site of uts1 and cn3 synthesis in the embryonic brain. uts1 Expression was confined to he midbrain tegmentum; distinct hindbrain cell groups, including locus oeruleus and Mauthner neurons; and the spinal cord. ucn3 Expression was ocalized to the optic tectum, serotonergic raphe, and distinct hombomeric cell clusters. The prominent expression of uts1 and ucn3 in rainstem is consistent with proposed roles of CRH-related peptides in tress-induced modulation of locomotor activity through monoaminergic rainstem neuromodulatory systems. J. Comp. Neurol. 518:2978-2995, 2010.
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29.
  • Capantini, L, et al. (författare)
  • The pretectal connectome in lamprey
  • 2017
  • Ingår i: The Journal of comparative neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 525:4, s. 753-772
  • Tidskriftsartikel (refereegranskat)
  •  
30.
  • Carlsson, Mikael A., et al. (författare)
  • Multiple neuropeptides in the Drosophila antennal lobe suggest complex modulatory circuits
  • 2010
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 518:16, s. 3359-3380
  • Tidskriftsartikel (refereegranskat)abstract
    • The fruitfly, Drosophila, is dependent on its olfactory sense in food search and reproduction. Processing of odorant information takes place in the antennal lobes, the primary olfactory center in the insect brain. Besides classical neurotransmitters, earlier studies have indicated the presence of a few neuropeptides in the olfactory system. In the present study we made an extensive analysis of the expression of neuropeptides in the Drosophila antennal lobes by direct profiling using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and immunocytochemistry. Neuropeptides from seven different precursor genes were unambiguously identified and their localization in neurons was subsequently revealed by immunocytochemistry. These were short neuropeptide F, tachykinin related peptide, allatostatin A, myoinhibitory peptide, SIFamide, IPNamide, and myosuppressin. The neuropeptides were expressed in subsets of olfactory sensory cells and different populations of local interneurons and extrinsic (centrifugal) neurons. In some neuron types neuropeptides were colocalized with classical neurotransmitters. Our findings suggest a huge complexity in peptidergic signaling in different circuits of the antennal lobe.
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31.
  • Chandrasekar, Gayathri, et al. (författare)
  • Distribution of corticotropin-releasing hormone in the developing zebrafish brain
  • 2007
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 505:4, s. 337-351
  • Tidskriftsartikel (refereegranskat)abstract
    • Corticotropin-releasing hormone (CRH) plays a central role in the physiological regulation of the hypothalamus-pituitary-adrenal/interrenal axis mediating endocrine, behavioral, autonomic, and immune responses to stress. Despite the wealth of knowledge about the physiological roles of CRH, the genetic mechanisms by which CRH neurons arise during development are poorly understood. As a first step toward analyzing the molecular and genetic pathways involved in CRH lineage specification, we describe the developmental distribution of CRH neurons in the embryonic zebrafish, a model organism for functional genomics and developmental biology. We searched available zebrafish expressed sequence tag (EST) databases for CRH-like sequences and identified one EST that contained the complete zebrafish CRH open reading frame (ORF). The CRH precursor sequence contained a signal peptide, the CRH peptide, and a cryptic peptide with a conserved sequence motif. RT-PCR analysis showed crh expression in a wide range of adult tissues as well as during embryonic and larval stages. By whole-mount in situ hybridization histochemistry, discrete crh-expressing cell clusters were found in different parts of the embryonic zebrafish brain, including telencephalon, preoptic region, hypothalamus, posterior tuberculum, thalamus, epiphysis, midbrain tegmentum, and rostral hindbrain and in the neural retina. The localization of crh mRNA within the preoptic region is consistent with the central role of CRH in the teleost stress response through activation of the hypothalamic-pituitary-interrenal axis. The widespread distribution of CRH-synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain.
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32.
  • Christensson, Maria, et al. (författare)
  • Time course of cerebellar morphological development in postnatal ferrets: Ontogenetic and comparative perspectives.
  • 2007
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 501:6, s. 916-930
  • Tidskriftsartikel (refereegranskat)abstract
    • We provide the first systematic description of the morphological ontogenesis of the ferret cerebellum and compare its relative time-course to that of the rat cerebellum. Overall cerebellar size, foliation, and thickness of cortical layers were quantified and Purkinje cell morphology was characterized at 24 timepoints in ferrets from postnatal day (P)1 to P63. The ferret cerebellum was substantially larger than that of the rat and had a much longer developmental period. In ferrets, Purkinje cells were dispersed into a monolayer by P9, the formation of folia declined abruptly around P20, and the external granular layer peaked in thickness around P22 and disappeared by P56. Timepoints of corresponding relative developmental maturity of the quantified architectural features of rat and ferret cerebella were determined and their relationship was analyzed by linear regression. The time-conversion equation derived, describing the relationship between cerebellar morphogenesis in the two species, had a determination coefficient (r2) of 0.95. Conspicuously, the equation predicted with high accuracy the timing of structural changes in individual Purkinje cells in the ferret cerebellum. The conversion equation should be useful for precise quantitative translation of data between studies of ferret and rat cerebellum and for comparisons between development of motor and sensory structures and functions in ferrets. The degree of similarity in the time-courses of cerebellar development in two distantly related mammals makes explicit in quantitative terms how remarkably conserved the cerebellum is in phylogenesis. Therefore, the methodology should be applicable to precise quantitative conversions of cerebellar developmental time-courses also between other species.
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33.
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34.
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35.
  • Davis, N T, et al. (författare)
  • Crustacean cardioactive peptide-immunoreactive neurons in the hawkmoth Manduca sexta and changes in their immunoreactivity during postembryonic development.
  • 1993
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 338:4, s. 612-27
  • Tidskriftsartikel (refereegranskat)abstract
    • An antiserum against crustacean cardioactive peptide was used, in indirect immunocytochemistry on whole-mounts and Vibratome sections, to map immunoreactive neurons at various stages of postembryonic development of the hawkmoth Manduca sexta. About 90 immunoreactive neurons were identified. Many of these cells are immunoreactive at hatching and persist into the adult stage; others become immunoreactive late in postembryonic development. During adult development, transient immunoreactivity is expressed in several cells in the subesophageal and thoracic ganglia. Two sets of immunoreactive neurons are found in the protocerebrum of larvae, but only one of these sets persists into the adult stage. Paired lateral interneurons and neurosecretory neurons are segmentally repeated in the abdominal ganglia and are present from the first larval stage to the adult; the abdominal interneurons project contralaterally to arborizations in adjacent ganglia, and some ascend to tritocerebral arborizations. The abdominal neurosecretory cells, which correspond to a pair of cells reported to contain bursicon, project posteriorly to neurohemal release organs. Motor neurons of dorsal external oblique abdominal muscles become immunoreactive in the fourth larval stage. Paired median neurosecretory cells of abdominal ganglia become immunoreactive during the fifth larval stage. The immunoreactive median and lateral abdominal neurosecretory cells are a subset of a group of cells known to contain cardioactive peptides. Paired lateral neurosecretory cells of the subesophageal ganglion become immunoreactive during pupation and project to the corpora cardiaca and aorta of the adult. Many of the neurons identified here are comparable to crustacean cardioactive peptide-immunoreactive cells described previously in locusts and the mealworm beetle.
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36.
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37.
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38.
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39.
  • Dircksen, Heinrich, 1954-, et al. (författare)
  • Ion transport peptide splice forms in central and peripheral neurons throughout postembryogenesis of Drosophila melanogaster.
  • 2008
  • Ingår i: The Journal of comparative neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 509:1, s. 23-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Ion transport peptides (ITPs) belong to a large arthropod neuropeptide family including crustacean hyperglycaemic hormones and are antidiuretic hormones in locusts. Because long and short ITP isoforms are generated by alternative splicing from a single gene in locusts and moths, we investigated whether similarly spliced gene products occur in the nervous system of Drosophila melanogaster throughout postembryogenesis. The itp gene CG13586 was reanalyzed, and we found three instead of the two previously annotated alternatively spliced mRNAs. These give rise to three different neuropeptides, two long C-terminally carboxylated isoforms (DrmITPL1 and DrmITPL2, both 87 amino acids) and one short amidated DrmITP (73 amino acids), which were partially identified biochemically. Immunocytochemistry and in situ hybridization reveal nine larval and 14 adult identified neurons: four pars lateralis neurosecretory neurons, three hindgut-innervating neurons in abdominal ganglia, and a stage-specific number of interneurons and peripheral bipolar neurons. The neurosecretory neurons persist throughout postembryogenesis, form release sites in corpora cardiaca, and invade corpora allata. One type of ITP-expressing interneuron exists only in the larval and prepupal subesophageal ganglia, whereas three types of interneurons in the adult brain arise in late pupae and invade circumscribed neuropils in superior median and lateral brain areas. One peripheral bipolar and putative sensory neuron type occurs in the larval, pupal, and adult preterminal abdominal segments. Although the neurosecretory neurons may release DrmITP and DrmITPL2 into the haemolymph, possible physiological roles of the hindgut-innervating and peripheral neurons as well as the interneurons are yet to be identified.
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40.
  • Dyakonova, Varvara, et al. (författare)
  • Anatomical basis for interactions of enkephalins with other transmitters in the CNS of a snail.
  • 1995
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 361, s. 38-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunocytochemical techniques for double staining were employed to investigate the morphological basis for interactions between enkephalins and other neuroactive compounds in the behavior of the gastropod mollusc Cepaea nemoralis. Coexistence of each of the two enkephalins with FMRFamide, serotonin or GABA-like immunoreactivity was found in certain neurons in cerebral, parietal, and pedal ganglia. Tyrosine hydroxylase-immunoreactive neurons were occasionally seen in close apposition to, but never colocalized with, the enkephalins. A comparison between these anatomical observations and previous behavioral studies suggests that in gastropod molluscs cotransmission of enkephalins with classical transmitters may, at least partly, reflect synergism of these substances in the control of definite behavioral programs
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41.
  • Eftekhari, Sajedeh, et al. (författare)
  • Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence and autoradiography.
  • 2016
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 524:1, s. 90-118
  • Tidskriftsartikel (refereegranskat)abstract
    • Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved.
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42.
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43.
  • Elofsson, Ulf O. E., et al. (författare)
  • Relationships between sex and the size and number of forebrain gonadotropin-releasing hormone-immunoreactive neurones in the ballan wrasse (Labrus berggylta), a protogynous hermaphrodite.
  • 1999
  • Ingår i: Journal of Comparative Neurology. - 0021-9967 .- 1096-9861. ; 410:1, s. 158-70
  • Tidskriftsartikel (refereegranskat)abstract
    • This study is the first to examine the brain gonadotropin-releasing hormone (GnRH) cell population phenotype in a protogynous and monandric sequentially hermaphroditic fish. Male ballan wrasse (Labrus berggylta) had on average higher numbers of GnRH-immunoreactive (GnRH-ir) cells within the brain preoptic area (POA) than females, a difference not found in GnRH-ir cells in other brain regions. Furthermore, in males, but not females, the number of these POA GnRH-ir cells correlated with body size. Maturational state (prespawning or postspawning) had marked effects on mean profile sizes (but not numbers) of both GnRH-ir cell bodies and cell nuclei, even when existing differences in body size and allometric relationships had been taken into account. Postspawning males tended to have larger GnRH-ir profiles in all brain regions relative to both prespawning males and females. Moreover, the GnRH-ir cell number in POA, and the cell body profile size in both POA and at the level of the anterior commissure, correlated with gonad size in spermiated prespawning males, indicating a relationship between both size and number of GnRH cells and male gonadal development. These results suggest that temporary changes in the size of brain GnRH-ir neurones are coupled to the male spawning cycle, and that permanent POA GnRH-ir cell number changes are involved in the process of sex change in sequential hermaphrodites. However, smaller males had no more preoptic GnRH-ir cells than equally sized females, which may argue against a proximate inducing role of GnRH cell number changes in naturally occurring sex reversal.
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44.
  • Enell, Lina, et al. (författare)
  • gamma-Aminobutyric acid (GABA) signaling components in Drosophila : immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter.
  • 2007
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 505:1, s. 18-31
  • Tidskriftsartikel (refereegranskat)abstract
    • γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in insects and is widely distributed in the central nervous system (CNS). GABA acts on ion channel receptors (GABAAR) for fast inhibitory transmission and on G-protein-coupled ones (GABABR) for slow and modulatory action. We used immunocytochemistry to map GABABR sites in the Drosophila CNS and compared the distribution with that of the GABAAR subunit RDL. To identify GABAergic synapses, we raised an antiserum to the vesicular GABA transporter (vGAT). For general GABA distribution, we utilized an antiserum to glutamic acid decarboxylase (GAD1) and a gad1-GAL4 to drive green fluorescent protein. GABABR-immunoreactive (IR) punctates were seen in specific patterns in all major neuropils of the brain. Most abundant labeling was seen in the mushroom body calyces, ellipsoid body, optic lobe neuropils, and antennal lobes. The RDL distribution is very similar to that of GABABR-IR punctates. However, the mushroom body lobes displayed RDL-IR but not GABABR-IR material, and there were subtle differences in other areas. The vGAT antiserum labeled punctates in the same areas as the GABABR and appeared to display presynaptic sites of GABAergic neurons. Various GAL4 drivers were used to analyze the relation between GABABR distribution and identified neurons in adults and larvae. Our findings suggest that slow GABA transmission is very widespread in the Drosophila CNS and that fast RDL-mediated transmission generally occurs at the same sites. J. Comp. Neurol. 505:18–31, 2007.
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45.
  • Engblom, David, 1975-, et al. (författare)
  • Activation of prostanoid EP3 and EP4 receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide
  • 2001
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 440:4, s. 378-386
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic inflammation activates central autonomic circuits, such as neurons in the pontine parabrachial nucleus. This activation may be the result of afferent signaling through the vagus nerve, but it may also depend on central prostaglandin-mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune challenge express prostaglandin receptors of the EP3 and EP4 subtypes, but it remains to be determined if the prostaglandin receptor-expressing neurons are identical to those that respond to immune stimuli. In the present study, bacterial wall lipopolysaccharide was injected intravenously in adult male rats and the expression of c-fos mRNA and of EP3 and EP4 receptor mRNA was examined with complementary RNA probes labeled with digoxigenin and radioisotopes, respectively. Large numbers of neurons in the external lateral parabrachial subnucleus, a major target of vagal-solitary tract efferents, expressed c-fos mRNA. Quantitative analysis showed that about 60% (range 40%–79%) of these neurons also expressed EP3 receptor mRNA. Conversely, slightly more than 50% (range 48%–63%) of the EP3 receptor-expressing neurons in the same subnucleus coexpressed c-fos mRNA. In contrast, few EP4 receptor-expressing neurons were c-fos positive, with the exception of a small population located in the superior lateral and dorsal lateral subnuclei. These findings show that immune challenge activates central autonomic neurons that could be the target of centrally produced prostaglandin E2, suggesting that synaptic signaling and paracrine mechanisms may interact on these neurons. J. Comp. Neurol. 440:378–386, 2001. © 2001 Wiley-Liss, Inc.
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46.
  • Engblom, David, 1975-, et al. (författare)
  • Induction of microsomal prostaglandin E synthase in the rat brain endothelium and parenchyma in adjuvant-induced arthritis
  • 2002
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 452:3, s. 205-214
  • Tidskriftsartikel (refereegranskat)abstract
    • Although central nervous symptoms such as hyperalgesia, fatigue, malaise, and anorexia constitute major problems in the treatment of patients suffering from chronic inflammatory disease, little has been known about the signaling mechanisms by which the brain is activated during such conditions. Here, in an animal model of rheumatoid arthritis, we show that microsomal prostaglandin E-synthase, the inducible terminal isomerase in the prostaglandin E2-synthesizing pathway, is expressed in endothelial cells along the blood-brain barrier and in the parenchyma of the paraventricular hypothalamic nucleus. The endothelial cells but not the paraventricular hypothalamic cells displayed a concomitant induction of cyclooxygenase-2 and expressed interleukin-1 type 1 receptors, which indicates that the induction is due to peripherally released cytokines. In contrast to cyclooxygenase-2, microsomal prostaglandin E synthase had very sparse constitutive expression, suggesting that it could be a target for developing drugs that will carry fewer side effects than the presently available cyclooxygenase inhibitors. These findings, thus, suggest that immune-to-brain communication during chronic inflammatory conditions involves prostaglandin E2-synthesis both along the blood-brain barrier and in the parenchyma of the hypothalamic paraventricular nucleus and point to novel avenues for the treatment of the brain-elicited disease symptoms during these conditions.
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47.
  • Engström, Linda, et al. (författare)
  • Systemic immune challenge induces preproenkephalin gene transcription in distinct autonomic structures of the rat brain
  • 2003
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 462:4, s. 450-461
  • Tidskriftsartikel (refereegranskat)abstract
    • The involvement of enkephalins in the immune response was investigated in rats injected intravenously with interleukin-1 (2 g/kg). In situ hybridization with a riboprobe complementary to intron A of the preproenkephalin (ppENK) gene showed distinct transcriptional activation within several brain regions known to be activated by immune stimuli, including the nucleus of the solitary tract, the area postrema, the paraventricular hypothalamic nucleus, and the oval nucleus of the bed nucleus of the stria terminalis, and dual labeling confirmed that a large proportion of the intron expressing neurons co-expressed c-fos mRNA. Rats injected with saline (controls) showed little or no heteronuclear transcript in these structures. The induced signal was strongest after 1 hour but was present in some structures 30 minutes after interleukin-1 injection. At 3 hours, transcriptional activity returned to basal levels. High basal expression of the heteronuclear transcript that appeared unchanged by the immune stimulus was seen in regions not primarily involved in the immune response, such as the striatum, the olfactory tubercle, and the islands of Calleja and in the immune activated central nucleus of the amygdala. The heteronuclear transcript colocalized with ppENK mRNA, demonstrating that it occurred in enkephalinergic neurons and was not the result of alternative transcription from the ppENK gene in other cells. These results demonstrated that enkephalin transcription is induced in central autonomic neurons during immune challenge, suggesting that enkephalins are involved in the centrally orchestrated response to such stimuli.
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48.
  • Enjin, Anders, et al. (författare)
  • Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells
  • 2010
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 518:12, s. 2284-2304
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal cholinergic neurons are critical for motor function in both the autonomic and somatic nervous systems and are affected in spinal cord injury and in diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Using two screening approaches and in situ hybridization, we identified 159 genes expressed in typical cholinergic patterns in the spinal cord. These include two general cholinergic neuron markers, one gene exclusively expressed in motor neurons and nine genes expressed in unknown subtypes of somatic motor neurons. Further, we present evidence that Chondrolectin (Chodl) is a novel genetic marker for putative fast motor neurons and that estrogen-related receptor b (ERRb) is a candidate genetic marker for slow motor neurons. In addition, we suggest paired-like homeodomain transcription factor 2 (Pitx2) as a marker for cholinergic partition cells.
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49.
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50.
  • Eskilsson, Anna, et al. (författare)
  • Distribution of microsomal prostaglandin E synthase-1 in the mouse brain
  • 2014
  • Ingår i: Journal of Comparative Neurology. - : John Wiley & Sons. - 0021-9967 .- 1096-9861. ; 522:14, s. 3229-3244
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies in rats have demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1) is induced in brain vascular cells that also express inducible cyclooxygenase-2, suggesting that such cells are the source of the increased PGE2 levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES-1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES-1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell-specific markers, we report that mPGES-1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary-associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES-1 in brain endothelial cells, but not in other mPGES-1-positive cells, was coexpressed with cyclooxygenase-2, whereas there was no coexpression between mPGES-1 and cyclooxygenase-1. These data imply a widespread synthesis of PGE2 or other mPGES-1-dependent products in the mouse brain that may be related to inflammation-induced sickness symptom as well as other functions, such as blood flow regulation.
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