| 1. |
- Björkman, Anders, et al.
(författare)
-
Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 2098-2106
-
Tidskriftsartikel (refereegranskat)abstract
- Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.
|
|
| 2. |
- Fuentes, Romulo, et al.
(författare)
-
Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:7, s. 1100-1108
-
Tidskriftsartikel (refereegranskat)abstract
- Specific motor symptoms of Parkinson's disease (PD) can be treated effectively with direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criteria. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but, from accumulated experience with the use of SCS in the management of chronic pain, it is known that the pathways most probably activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS results from direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brainstem nuclei, contributing to the initiation of locomotion. On the basis of the striking change in the corticostriatal oscillatory mode of neuronal activity induced by SCS, we propose that, through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low-frequency (< 30 Hz) oscillatory synchronization in the corticobasal ganglia circuits.
|
|
| 3. |
- Gabery, Sanaz, et al.
(författare)
-
Characterization of a rat model of Huntington's disease based on targeted expression of mutant huntingtin in the forebrain using adeno-associated viral vectors.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:6, s. 2789-2800
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (htt) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant htt is ubiquitously expressed, it has not been possible to establish clear structure-to-function relationships for the clinical aspects. In the present study, we have injected recombinant adeno-associated viral vectors of serotype 5 (rAAV5) expressing an 853-amino-acid fragment of htt with either 79 (mutant) or 18 (wild-type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of htt in the forebrain. Rats were followed for 6 months and compared with control rats. Neuropathological assessment showed long-term expression of the green fluorescent protein (GFP) transgene (used as a marker protein) and accumulation of htt inclusions in the cerebral cortex with the rAAV5-htt-79Q vectors. We estimated that around 10% of NeuN-positive cells in the cerebral cortex and 2% of DARPP-32 neurons in the striatum were targeted with the GFP-expressing vector. Formation of intracellular htt inclusions was not associated with neuronal loss, gliosis or microglia activation and did not lead to altered motor activity or changes in body weight. However, the same mutant htt vector caused orexin loss in the hypothalamus - another area known to be affected in HD. In conclusion, our results demonstrate that widespread forebrain expression of mutant htt can be achieved using rAAV5-vectors and suggest that this technique can be further explored to study region-specific effects of mutant htt or other disease-causing genes in the brain.
|
|
| 4. |
- Grealish, Shane, et al.
(författare)
-
Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease.
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; Jul 1, s. 2266-2278
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (>/= 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.
|
|
| 5. |
- Kallur, Therese, et al.
(författare)
-
Spatio-temporal dynamics, differentiation and viability of human neural stem cells after implantation into neonatal rat brain.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 34, s. 382-393
-
Tidskriftsartikel (refereegranskat)abstract
- Neural stem cells (NSCs) have attracted major research interest due to their potential use in cell replacement therapy. In patients, human cells are the preferred choice, one source of human NSCs being the brain of fetuses. The aims of the present study were to explore the long-term differentiation, mobility and viability of NSCs derived from the human fetal striatum in response to intracerebral implantation. To investigate long-term spatio-temporal and functional dynamics of grafts in vivo by magnetic resonance imaging, these cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles prior to implantation. SPIO-labeling of human NSCs left the quantitative profile of the proliferation, cell composition and differentiation capacity of the cells in vitro unaltered. Also after transplantation, the phenotypes after long-term cell differentiation were not significantly different from naïve cells. Upon transplantation, we detected a hypointensity corresponding to the striatal graft location in all animals and persisting for at least 4 months. The hypointense signal appeared visually similar both in location and in volume over time. However, quantitative volumetric analysis showed that the detectable, apparent graft volume decreased significantly from 3 to 16 weeks. Finally, the human NSCs were not proliferating after implantation, indicating lack of tumor formation. These cells are thus a promising candidate for translationally relevant investigations for stem cell-based regenerative therapies.
|
|
| 6. |
- Kokaia, Merab
(författare)
-
Seizure-induced neurogenesis in the adult brain.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33:6, s. 1133-1138
-
Tidskriftsartikel (refereegranskat)abstract
- It is well established that seizures increase adult neurogenesis in the subventricular and subgranular zones, the most neurogenic regions of the adult rodent and apparently human brain. However, the role of increased neurogenesis in these areas in seizure generation (ictogenesis) and epileptogenesis remains elusive. It is of utmost importance to explore how the cells that are born in response to epileptic seizures are functionally integrated into the existing neuronal networks, and how this integration would contribute to the excitability of this network. This will determine whether increased neurogenesis is beneficial or counteractive to ictogenesis and epileptogenesis. Some of the crucial factors affecting the functional integration of newborn cells seem to be excessive neuronal activity and/or inflammatory microenvironment, both associated with acute, as well as chronic, epileptic conditions. This review will focus on aspects of the functional integration of newborn cells in animal models of epilepsy with various degrees of seizure severity and associated microenvironmental alterations in the brain tissue.
|
|
| 7. |
- Ledri, Marco, et al.
(författare)
-
Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 1971-1983
-
Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditions, the endogenous excitability regulator neuropeptide Y (NPY) has been shown to modulate afferent inputs onto dentate gyrus CCK-basket cells, providing a possible novel mechanism for excitability control in the hippocampus. Using GAD65-GFP mice for CCK-basket cell identification, and whole-cell patch-clamp recordings, we explored whether the effect of NPY on afferent synapses to CCK-basket cells is modified in the hyper-excitable dentate gyrus. To induce a hyper-excitable state, recurrent seizures were evoked by electrical stimulation of the hippocampus using the well-characterized rapid kindling protocol. The frequency of spontaneous and miniature excitatory and inhibitory post-synaptic currents recorded in CCK-basket cells was decreased by NPY. The excitatory post-synaptic currents evoked in CCK-basket cells by optogenetic activation of principal neurons were also decreased in amplitude. Interestingly, we observed an increased proportion of spontaneous inhibitory post-synaptic currents with slower rise times, indicating that NPY may inhibit gamma aminobutyric acid release preferentially in peri-somatic synapses. These findings indicate that increased levels and release of NPY observed after seizures can modulate afferent inputs to CCK-basket cells, and therefore alter their impact on the oscillatory network activity and excitability in the hippocampus.
|
|
| 8. |
- Ulusoy, Ayse, et al.
(författare)
-
Co-expression of C-terminal truncated alpha-synuclein enhances full-length alpha-synuclein-induced pathology.
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:3, s. 409-422
-
Tidskriftsartikel (refereegranskat)abstract
- Lewy bodies, which are a pathological hallmark of Parkinson's disease, contain insoluble polymers of alpha-synuclein (alphasyn). Among the different modifications that can promote the formation of toxic alphasyn species, C-terminal truncation is among the most abundant alterations in patients with Parkinson's disease. In vitro, C-terminal truncated alphasyn aggregates faster and sub-stoichiometric amounts of C-terminal truncated alphasyn promote aggregation of the full-length alphasyn (alphasynFL) and induce neuronal toxicity. To address in vivo the putative stimulation of alphasyn-induced pathology by the presence of truncated alphasyn, we used recombinant adeno-associated virus to express either alphasynFL or a C-terminal truncated alphasyn (1-110) in rats. We adjusted the recombinant adeno-associated virus vector concentrations so that either protein alone led to only mild to moderate axonal pathology in the terminals of nigrostriatal dopamine neurons without frank cell loss. When these two forms of alphasyn were co-expressed at these pre-determined levels, it resulted in a more aggressive pathology in fiber terminals as well as dopaminergic cell loss in the substantia nigra. Using an antibody that did not detect the C-terminal truncated alphasyn (1-110) but only alphasynFL, we demonstrated that the co-expressed truncated protein promoted the progressive accumulation of alphasynFL and formation of larger pathological accumulations. Moreover, in the co-expression group, three of the eight animals showed apomorphine-induced turning, suggesting prominent post-synaptic alterations due to impairments in the dopamine release, whereas the mild pathology induced by either form alone did not cause motor abnormalities. Taken together these data suggest that C-terminal truncated alphasyn can interact with and exacerbate the formation of pathological accumulations containing alphasynFL in vivo.
|
|
| 9. |
- Weibull, Andreas, et al.
(författare)
-
Cerebral and clinical effects of short-term hand immobilisation.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33, s. 699-704
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, functional changes in the sensorimotor cortex following unilateral hand immobilisation were investigated in 11 healthy volunteers. Sensory and motor function of both hands was also assessed. Cortical activation was monitored with functional magnetic resonance imaging at 3 T. All examinations were performed prior to and directly after 72 h of immobilisation of the dominant hand and wrist. Following unilateral immobilisation, cortical activation increased substantially during tactile stimulation of the non-immobilised hand. This was particularly evident in the ipsilateral somatosensory cortex. Additionally, a redistribution of hemispheric dominance towards zero lateralisation was seen. A bilateral cortical activation increase was also seen during performance of a finger-tapping task by the non-immobilised hand, although this increase was less prominent than during tactile stimulation. In contrast, performance of the finger-tapping task with the immobilised hand resulted in an activation decrease, predominantly in the ipsilateral sensorimotor cortex. This site was anatomically close to the regional activation increase of the non-immobilised hand. These functional changes were associated with reduced grip strength, dexterity and tactile discrimination of the immobilised hand, and simultaneously improved tactile discrimination of the non-immobilised hand. This suggests that brain adaptation following hand immobilisation includes inter-hemispheric dynamics. In summary, the improved sensory function of the non-immobilised hand following unilateral immobilisation is associated with cortical expansion, predominantly contralateral to the immobilised hand, and a redistribution of hemispheric dominance. Both cortical and clinical effects of immobilisation were identified after 72 h, suggesting rapid inter-hemispheric plasticity using existing neural substrates.
|
|
| 10. |
- Zapka, Manuela, et al.
(författare)
-
Night-time neuronal activation of Cluster N in a day- and night-migrating songbird
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:4, s. 619-624
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetic compass orientation in a night-migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night-migrants performing magnetic compass-guided behaviour at night, whereas no activation is observed during the day, and covering up the birds' eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light-dependent magnetic compass information in night-migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day- and night-migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim-light at night, but not under full room-light conditions during the day. These data suggest that, in day- and night-migratory meadow pipits, the light-dependent magnetic compass, which requires an active Cluster N, may only be used during night-time, whereas another magnetosensory mechanism and/or other reference system(s), like the sun or polarized light, may be used as primary orientation cues during the day.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Harkany, T
(författare)
-
Molecular mechanisms of neuronal specification
- 2011
-
Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 34:10, s. 1513-1515
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 14. |
|
|
| 15. |
- Koivisto, Mika, et al.
(författare)
-
Unconscious response priming by shape depends on geniculostriate visual projection
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley-Blackwell. - 0953-816X .- 1460-9568. ; 35:4, s. 623-633
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that unconscious visual processing of some stimulus features might occur without the contribution of early visual cortex (V1/V2). In the present study, the causal role of V1/V2 in unconscious processing of simple shapes in intact human brain was studied by applying transcranial magnetic stimulation (TMS) on early visual cortex or lateral occipital cortex (LO) while observers performed a metacontrast-masked response priming task with arrow figures as visual stimuli. Magnetic stimulation of V1/V2 impaired masked priming 3090 ms after the onset of the prime. Stimulation of LO reduced the magnitude of masked priming at 90120 ms, but this effect occurred only in the early parts of the priming experiment. A control task measuring the visibility of masked primes indicated that the orientation of masked primes could not be consciously discriminated and that TMS did not influence the conscious visibility of the primes indirectly by reducing the effectiveness of the mask in the critical time windows. We conclude that feedforward sweep of processing from V1/V2 (3090 ms) to LO (90 ms and above) is necessary for unconscious priming of shape, whereas conscious perception requires also the contribution of recurrent (feedback) processing.
|
|
| 16. |
- Mulder, Jan, et al.
(författare)
-
Secretagogin is a Ca2+-binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 31:12, s. 2166-2177
-
Tidskriftsartikel (refereegranskat)abstract
- The Ca2+-binding proteins (CBPs) calbindin D28k, calretinin and parvalbumin are phenotypic markers of functionally diverse subclasses of neurons in the adult brain. The developmental dynamics of CBP expression are precisely timed: calbindin and calretinin are present in prospective cortical interneurons from mid-gestation, while parvalbumin only becomes expressed during the early postnatal period in rodents. Secretagogin (scgn) is a CBP cloned from pancreatic beta and neuroendocrine cells. We hypothesized that scgn may be expressed by particular neuronal contingents during prenatal development of the mammalian telencephalon. We find that scgn is expressed in neurons transiting in the subpallial differentiation zone by embryonic day (E)11 in mouse. From E12, scgn+ cells commute towards the extended amygdala and colonize the bed nucleus of stria terminalis, the interstitial nucleus of the posterior limb of the anterior commissure, the dorsal substantia innominata (SI) and the central and medial amygdaloid nuclei. Scgn+ neurons can acquire a cholinergic phenotype in the SI or differentiate into GABA cells in the central amygdala. We also uncover phylogenetic differences in scgn expression as this CBP defines not only neurons destined to the extended amygdala but also cholinergic projection cells and cortical pyramidal cells in the fetal nonhuman primate and human brains, respectively. Overall, our findings emphasize the developmentally shared origins of neurons populating the extended amygdala, and suggest that secretagogin can be relevant to the generation of functional modalities in specific neuronal circuitries.
|
|
| 17. |
- Salomé, Nicolas, et al.
(författare)
-
Gastrectomy alters emotional reactivity in rats: neurobiological mechanisms.
- 2011
-
Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33:9, s. 1685-95
-
Tidskriftsartikel (refereegranskat)abstract
- Gastrectomy (Gsx) is associated with altered emotional function and a predisposition to depression/anxiety disorders. Here we investigated the effects of Gsx on emotional reactivity in rats and explored the underlying neurobiological mechanisms. Gsx- and sham-operated rats were exposed to behavioural tests that explore anxiety- and depression-like behaviour (open field, black and white box, elevated plus maze, social interaction, forced swim) as well as memory (object recognition). The potential neurobiological mechanisms underlying these differences were explored by measuring (i) turnover of candidate neurotransmitter systems in the nucleus accumbens, (ii) hippocampal neurogenesis by BrdU labelling or by analysis of candidate genes involved in neuronal growth and (iii) changes in mRNA expression of candidate genes in dissected hippocampal and amygdala tissue. Data from individual behavioural tests as well as from multivariate analysis revealed differing emotional reactivity between Gsx- and sham-operated rats. Gsx rats showed reduced emotional reactivity in a new environment and decreased depression-like behaviour. Accumbal serotonin and dopamine turnover were both reduced in Gsx rats. Gsx also led to a memory deficit, although hippocampal neurogenesis was unaffected. Of the many candidate genes studied by real-time RT-PCR, we highlight a Gsx-associated decrease in expression of Egr-1, a transcription factor linked to neural plasticity and cognition, in the hippocampus and amygdala. Thus, Gsx induces an alteration of emotional reactivity and a memory/cognitive deficit that is associated with reduced turnover of serotonin and dopamine in the nucleus accumbens and decreased expression of Egr-1 in the hippocampus and amygdala.
|
|
| 18. |
- Stout, Dietrich, et al.
(författare)
-
Technology, expertise, and social cognition in human evolution
- 2011
-
Ingår i: European Journal of Neuroscience. - Oxford : Wiley-Blackwell. - 0953-816X .- 1460-9568. ; 33:7, s. 1328-1338
-
Tidskriftsartikel (refereegranskat)abstract
- Paleolithic stone tools provide concrete evidence of major developments in human behavioural and cognitive evolution. Of particular interest are evolving cognitive mechanisms implied by the cultural transmission of increasingly complex prehistoric technologies, hypothetically including motor resonance, causal reasoning and mentalizing. To test the relevance of these mechanisms to specific Paleolithic technologies, we conducted a functional magnetic resonance imaging study of Naı¨ve, Trained and Expert subjects observing two toolmaking methods of differing complexity and antiquity: the simple ‘Oldowan’ method documented by the earliest tools 2.5 million years ago; and the more complex ‘Acheulean’ method used to produce refined tools 0.5 million years ago. Subjects observed 20-s video clips of an expert demonstrator, followed by behavioural tasks designed to maintain attention. Results show that observational understanding of Acheulean toolmaking involves increased demands for the recognition of abstract technological intentions. Across subject groups, Acheulean compared with Oldowan toolmaking was associated with activation of left anterior intraparietal and inferior frontal sulci, indicating the relevance of resonance mechanisms. Between groups, Naïve subjects relied on bottom-up kinematic simulation in the premotor cortex to reconstruct unfamiliar intentions, and Experts employed a combination of familiarity-based sensorimotor matching in the posterior parietal cortex and top-down mentalizing involving the medial prefrontal cortex. While no specific differences between toolmaking technologies were found for Trained subjects, both produced frontal activation relative to Control, suggesting focused engagement with toolmaking stimuli. These findings support motor resonance hypotheses for the evolutionary origins of human social cognition and cumulative culture, directly linking these hypotheses with archaeologically observable behaviours in prehistory.
|
|
| 19. |
|
|
| 20. |
- Berube-Carriere, Noemie, et al.
(författare)
-
Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 35:4, s. 527-538
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual THVGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
|
|
| 21. |
|
|
| 22. |
- Clausen, Fredrik, et al.
(författare)
-
Neutralization of interleukin-1 beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 34:1, s. 110-123
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that interleukin-1 beta (IL-1 beta) is a key mediator of the inflammatory response following traumatic brain injury (TBI). Recently, we showed that intracerebroventricular administration of an IL-1 beta-neutralizing antibody was neuroprotective following TBI in mice. In the present study, an anti-IL-1 beta antibody or control antibody was administered intraperitoneally following controlled cortical injury (CCI) TBI or sham injury in 105 mice and we extended our histological, immunological and behavioral analysis. First, we demonstrated that the treatment antibody reached target brain regions of brain-injured animals in high concentrations (> 11 nm) remaining up to 8 days post-TBI. At 48 h post-injury, the anti-IL-1b treatment attenuated the TBI-induced hemispheric edema (P < 0.05) but not the memory deficits evaluated using the Morris water maze (MWM). Neutralization of IL-1 beta did not influence the TBI-induced increases (P < 0.05) in the gene expression of the Ccl3 and Ccr2 chemokines, IL-6 or Gfap. Up to 20 days post-injury, neutralization of IL-1 beta was associated with improved visuospatial learning in the MWM, reduced loss of hemispheric tissue and attenuation of the microglial activation caused by TBI (P < 0.05). Motor function using the rotarod and cylinder tests was not affected by the anti-IL-1 beta treatment. Our results suggest an important negative role for IL-1 beta in TBI. The improved histological and behavioral outcome following anti-IL-1 beta treatment also implies that further exploration of IL-1 beta-neutralizing compounds as a treatment option for TBI patients is warranted.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
