| 1. |
- Clarke, D J, et al.
(författare)
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Synaptic connections formed by grafts of different types of cholinergic neurons in the host hippocampus
- 1990
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 107:1, s. 11-22
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Tidskriftsartikel (refereegranskat)abstract
- The present experiment was performed to determine whether different types of grafted central cholinergic neurons are able to form synaptic contacts with host hippocampal neurons. Grafts from the septal-diagonal band area, which contain the neurons that normally innervate the hippocampal formation, were compared to those from the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brain stem, and the spinal cord. The regions were dissected from 14- to 16-day-old rat fetuses, and the same number of viable cells (35 x 10(4] from each of the different regions was stereotaxically injected as a cell suspension into the hippocampus of rats subjected to a complete fimbria-fornix lesion, transecting the intrinsic septohippocampal pathways. At 14 to 17 weeks after transplantation, the brains were processed for choline acetyltransferase (ChAT) immunocytochemistry at the light and electron microscopic levels and acetylcholinesterase (AChE) histochemistry at the light microscopic level. There was a great variation in the number of surviving ChAT-positive cells among the different graft types. The septal grafts contained the highest number of ChAT-positive cells, and the striatal grafts showed the lowest numbers. The NBM, brain stem, and spinal cord grafts were in between. The differences in the number of ChAT-positive neurons between the groups matched, in general, the differences found in the magnitude of graft-derived AChE-positive fiber growth into the host hippocampal formation. At the electron microscopical level, all types of grafts were capable of forming synaptic contacts with host elements, however, with vast differences in the number of synapses found. The septal grafts produced the highest number of contacts, whereas the striatal and spinal cord grafts produced very few contacts. The ultrastructure of the cholinergic fibers from grafts obtained from the forebrain areas, i.e., septum, NBM, and striatum all appeared normal, whereas brain stem and spinal cord grafts produced different types of anomalies. The results show that grafted cholinergic neurons, that normally do not innervate the hippocampus, can send axons and form synaptic contacts in the host hippocampus. The ability to reinnervate the denervated hippocampal target appears to be shared by the embryologically closely related forebrain cholinergic neuron types, i.e., the septal, NBM, and striatal neurons. The marked differences in overall fiber ingrowth and number of synapses observed between these different types of grafts could be explained largely on the basis of differences in survivability of each grafted neuron type. By contrast, the reinnervation obtained from the grafted brain stem and spinal cord neurons were both quantitatively and qualitatively abnormal.(ABSTRACT TRUNCATED AT 400 WORDS)
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| 2. |
- Dahlin, L B, et al.
(författare)
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Axonal growth in mesothelial chambers : effects of a proximal preconditioning lesion and/or predegeneration of the distal nerve stump
- 1988
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 99:3, s. 63-655
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Tidskriftsartikel (refereegranskat)abstract
- Preformed, autologous mesothelial chambers were utilized to study axonal growth following selective predegeneration of the distal nerve stump and/or preconditioning of the proximal nerve stump. The left and/or right sciatic nerve of rats was exposed and transected in the thigh. Two weeks after transection, the left proximal nerve stump was cross-anastomosed with the right distal nerve stump by using a mesothelial chamber leaving a 15-mm gap between the two nerve stumps. Previous studies have shown that axonal overgrowth normally does not occur over this gap distance to the distal stump. Three months after cross-anastomosing, regeneration across the 15-mm gap was evaluated by muscle action potential recordings and light microscopical examination. In experiments in which a distal nerve stump was selectively degenerated and the proximal segment was freshly cut, axons had bridged the 15-mm gap in six of seven rats. When a proximal preconditioned nerve stump was matched with a freshly cut distal stump, axonal overgrowth occurred in only 4 of 10 experiments. In experiments including a proximal preconditioned nerve stump and a distal predegenerated stump, axons bridged the gap in 6 of 8 experiments. We concluded that a priming lesion, including manipulation with proximal and/or distal stump, enhances axonal growth in mesothelial chambers.
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| 3. |
- Danielsen, N, et al.
(författare)
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Experimental hyperthyroidism stimulates axonal growth in mesothelial chambers
- 1986
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 94:1, s. 54-65
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Tidskriftsartikel (refereegranskat)abstract
- An experimental model is presented for studying axonal growth after experimental hyperthyroidism and hypothyroidism. The left sciatic nerve of the rat was transected and transposed to the back. The proximal nerve stump was inserted into a 50-mm-long mesothelial chamber leaving the distal end of the chamber open. Different groups of young adult rats were given daily injections of thyroxine (10 micrograms/100 g body weight) or the goitrogen, thiamazol, in the drinking water (0.125 g/liter) for 12 weeks. Thyroxine treatment increased significantly the extent of axonal outgrowth from the proximal nerve stump compared with untreated rats. Experimental hypothyroidism (thiamazol treatment), evidenced by a retarded body growth, did not affect the extent of axonal outgrowth. In other experiments the left proximal nerve stump was cross-anastomosed with the right distal nerve stump. The two nerve stumps were bridged with a mesothelial chamber leaving a 15-mm gap. This gap distance is known from our previous studies to inhibit axonal overgrowth to the distal nerve stump. As evidenced by histological evaluation, in three of six thyroxine-treated rats, axons had bridged the 15-mm gap. We conclude that experimentally induced hyperthyroidism enhances axonal growth in mesothelial chambers.
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| 4. |
- Doering, L C, et al.
(författare)
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Abnormal perikaryal immunoreactivity to the phosphorylated heavy neurofilament unit in intracerebral basal forebrain transplants
- 1991
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Ingår i: Experimental Neurology. - 0014-4886. ; 111:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Grafts of Embryonic Day 14-15 basal forebrain tissue (medial septal/diagonal band nuclei) were transplanted into an aspirative fimbria-fornix cavity or the hippocampus of young adult rats. After extended periods of survival (1 and 2 years) the grafts were examined with immunocytochemical probes to identify specific types of neurons and assess the (spatial) distribution of the phosphorylated heavy neurofilament protein. Subpopulations of the long-term transplanted neurons expressed immunoreactivity to choline acetyl-transferase (CAT) and the low-affinity nerve growth factor receptor (192-IgG). Axons from the grafted neurons, visualized with the monoclonal antibody RT97 to the Mr 200,000 phosphorylated neurofilament unit, were observed to extend over the surfaces of the brain and connect with the host hippocampus. In subgroups of neurons without apparent axonal connections to the hippocampus, a change from axonal to cell body RT97 immunoreactivity was evident. A population of these neurons with abnormal neurofilament immunostaining in the soma was simultaneously identified as cholinergic with the CAT antibody. These studies indicate that abnormal changes can develop in the cytoskeleton of neurons in long-term intracerebral septal transplants. Although the reasons for this type of neurofilament modification in the grafted neurons are unknown, inappropriate terminal connections may be an important factor in the expression of this cytoskeletal change.
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| 5. |
- Ekström, Peter, et al.
(författare)
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A morphometric study of age-related changes in serotonin-immunoreactive cell groups in the brain of the coho salmon, Oncorhynchus kisutch walbaum
- 1992
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Ingår i: Experimental Neurology. - 0014-4886. ; 116:2, s. 204-209
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Tidskriftsartikel (refereegranskat)abstract
- In the coho salmon there is a transient increase in total brain concentrations of serotonin during smolt transformation which occurs midlife, just before down-stream migration to the ocean. There is also a gradual age-related increase in total brain serotonin concentrations. These increases may be due to reorganization of the central serotonergic system, changes in serotonin turnover, or both. They may be related to the specific physiological conditions during different life stages of salmon, or to ongoing growth and plastic changes of the brain. In the present study we have compared serotonin-immunoreactive (5-HTir) cell groups in 1-year-old freshwater presmolt and 2-year-old seawater postsmolt salmon. Our data indicate a continuous growth of the 5-HTir cell groups in terms of an increase in numbers of 5-HTir neurons in the cell groups of the pretectum and the brain stem, and an increase in the volumes of such neurons and cell groups. However, when related to the increase in total brain volume, i.e., the volume that may be innervated by the 5-HTir neurons, the ratio of 5-HTir neurons per mm3 decreased. The largest decreases were observed in the median raphe nucleus (P < 0.005) and the B9 group (P < 0.05). The ratio of volumes of the brain nuclei containing 5-HTir neurons relative to total brain volume was remarkably constant when comparing pre- and postsmolt brains: only the pretectal nucleus showed a significant decrease (P < 0.01) in relative volume. The total volume of 5-HTir neurons increased in postsmolts (P < 0.005). Since there was no increase in size of 5-HTir somata in any nucleus, changes in total volume reflect the changes in numbers of 5-HTir neurons. Thus, to account for the observed age-related increase in total brain concentrations of serotonin, an increase in the net production of serotonin, possibly accompanied by an increase in the density of serotonergic innervation in certain brain areas, may be postulated. The transient surge of whole brain content of serotonin observed at smolt transformation probably reflects a transient change in serotonin metabolism rather than an increase in the number of neurons.
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| 6. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Neuronal differentiation following transplantation of expanded mouse neurosphere cultures derived from different embryonic forebrain regions.
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 184:2, s. 615-635
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Tidskriftsartikel (refereegranskat)abstract
- In vitro, expanded neurospheres exhibit multipotent properties and can differentiate into neurons, astrocytes and oligodendrocytes. In vivo, cells from neurospheres derived from mouse fetal forebrain have previously been reported to predominantly differentiate into glial cells, and not into neurons. Here we isolated stem/progenitor cells from E13.5 lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE) and cortical primordium, of a green fluorescent protein (GFP)-actin transgenic mouse. Free-floating neurospheres were expanded in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and implanted after five to six passages into the striatum, hippocampus and cortex of neonatal rats. Cell suspensions of primary LGE tissue were prepared and grafted in parallel. Grafted cells derived from the primary tissue displayed widespread incorporation into all regions, as visualized with the mouse-specific antibody M2, or mouse satellite DNA in situ hybridization, and differentiated into both neurons, astrocytes and oligodendrocytes. Grafts of neurosphere cells derived from the LGE, MGE and cortical primordium differentiated primarily into astrocytes, but contained low but significant numbers of GFP-immunoreactive neurons. Neurons derived from LGE neurospheres were of three types: cells with the morphology of medium-sized densely spiny projection neurons in the striatum; cells with interneuron-like morphologies in striatum, cortex and hippocampus; and cells integrating into SVZ and migrating along the RMS to the olfactory bulb. MGE- or cortical primordium-derived neurospheres differentiated into interneuron-like cells in both striatum and hippocampus. The results demonstrate the ability of in vitro expanded neural stem/progenitor cells to generate both neurons and glia after transplantation into neonatal recipients, and differentiate in a region-specific manner into mature neurons with morphological features characteristic for each target site.
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| 7. |
- Grabowski, Martin, et al.
(författare)
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Fetal neocortical grafts implanted in adult hypertensive rats with cortical infarcts following a middle cerebral artery occlusion: ingrowth of afferent fibers from the host brain
- 1992
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Ingår i: Experimental Neurology. - 0014-4886. ; 116:2, s. 105-121
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Tidskriftsartikel (refereegranskat)abstract
- This study is focused on the survival of fetal neocortical grafts placed in the infarcted adult host cortex of the spontaneously hypertensive rat and describes the ability of host axonal regeneration into the graft after a focal ischaemic lesion. Five to seven days following ligation of the right middle cerebral artery, dissociated neocortical primordium from fetuses of gestational age 12-18 days was implanted into the infarcted cortical area. Surviving transplants were seen in all rats, although grafts derived from gestational age 12-14 days displayed an irregular morphology rich in sinusoid-like cavities and containing fewer cells of apparently mature neuronal morphology. Grafts from older donors contained perikarya of neuronal appearance; however, they lacked normal cortical lamination. Ten days postgrafting, fibers stained by acetylcholinesterase histochemistry, dopamine-beta-hydroxylase, and 5-hydroxytryptamine immunohistochemistry were found in the grafts, and by 10-23 weeks after transplantation the fiber density had increased substantially. When the retrograde tracer Fluoro-Gold was injected into the grafted tissue, labeled cells were found in several subcortical nuclei of the host, including the nucleus basalis of Meynert, ventral pallidum, thalamus, dorsal raphe, locus coeruleus, as well as the ipsilateral and contralateral neocortex. This study shows that grafts of dissociated neocortical tissue exhibit good survival and growth potential when implanted into infarcted neocortex and that several nerve fiber systems of the adult host have a regenerative capacity sufficient to innervate the grafted tissue.
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| 8. |
- Grover, A, et al.
(författare)
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A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 184:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau.
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| 9. |
- Lindvall-Axelsson, Maria, et al.
(författare)
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Inhibition of cerebrospinal fluid formation by omeprazole
- 1992
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 115:3, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
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| 10. |
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| 11. |
- Maciel, EN, et al.
(författare)
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Cyclosporin A and Bcl-2 do not inhibit quinolinic acid-induced striatal excitotoxicity in rodents
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 183:2, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in addition Bcl-2 also inhibits apoptotic stimuli-mediated release of mitochondrial apoptogenic factors. Isolated brain mitochondria from cyclosporin A-treated rats showed resistance to Ca2+-induced dissipation of the membrane potential, indicating protection against MPT. We conclude that quinolinic acid-mediated striatal excitotoxicity is not dependent on MPT and Bcl-2-sensitive apoptotic cell death pathways. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 12. |
- Nanobashvili, Z, et al.
(författare)
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Suppression of limbic motor seizures by electrical stimulation in thalamic reticular nucleus
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 181:2, s. 224-230
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Tidskriftsartikel (refereegranskat)abstract
- Kindling is a model of temporal lobe epilepsy in which repeated electrical stimulations in limbic areas lead to progressive increase of seizure susceptibility, culminating in generalized convulsions and the establishment of a permanent epileptic syndrome. We studied here the effect of stimulations in the thalamic reticular nucleus (TRN) on. the development of seizures and hippocampal hyperexcitability in kindling elicited from the ventral hippocampus in rats. Animals given 12 kindling stimulations per day with 30-min intervals for 4 consecutive days developed generalized convulsions on day 4. Stimulations in TRN delivered simultaneously with those in the hippocampus induced marked suppression of seizure generalization. Similarly, the number of generalized seizures and the duration of behavioral convulsions were reduced when rats subjected to 40 kindling stimulations with 5-min intervals during about 3 h were costimulated in the TRN. The anticonvulsant effect of TRN costimulation was detected also when rats were test-stimulated in the hippocampus at 24 h and 2 and 4 weeks after the initial 40 hippocampal stimulations. Our data provide the first evidence that TRN stimulations can act to suppress limbic motor seizures in hippocampal kindling and suggest a new approach for seizure control in temporal lobe epilepsy. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 13. |
- Olsson, A, et al.
(författare)
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Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 183, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Povlsen, Bo, et al.
(författare)
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Functional evaluation of regenerated and misrouted axons to glabrous and hairy skin of the rat hind foot after sciatic neurotomy and suture
- 1995
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 132:1, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- The function of misrouted regenerated polymodal nociceptor C-fibers and low-threshold mechanoreceptive axons in the lateral plantar nerve (LPN) and in the foot branch of the superficial peroneal nerve (fSPN) was evaluated 3 months after unilateral sciatic neurotomy and suture. Two weeks before evaluation the tibial fascicle (or the peroneal fascicle) above the neurotomy was cut and tied off. In this way only functional regeneration of misrouted axons was tested in the LPN (or the fSPN). In regenerated animals the glabrous skin area had no functional fSPN-related low-threshold mechanoreceptive axons. However, the hairy fSPN skin area showed function of misrouted LPN-related low-threshold mechanoreceptive axons. In both the glabrous skin domain innervated by the LPN and the hairy skin area supplied by the fSPN, functional regeneration of misrouted polymodal nociceptor C-fibers was found. We conclude that functional regeneration of misrouted axons related to polymodal nociceptive units and low-threshold mechanoreceptive units is more efficient in hairy skin of the rat foot whereas only misrouted polymodal nociceptor C-fibers recover function in glabrous skin.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Andersson, Daniel, et al.
(författare)
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Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.
- 2010
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Ingår i: Experimental neurology. - : Elsevier BV. - 1090-2430 .- 0014-4886. ; 221:1, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.
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| 34. |
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| 35. |
- Andsberg, Gunnar, et al.
(författare)
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Upregulation of p75 neurotrophin receptor after stroke in mice does not contribute to differential vulnerability of striatal neurons
- 2001
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 169:2, s. 351-363
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Tidskriftsartikel (refereegranskat)abstract
- The survival of different neuron types and the expression of the p75 neurotrophin receptor (p75(NTR)) after focal cerebral ischemia were studied in the mouse striatum using immunocytochemical and histochemical techniques and stereological procedures. As assessed at 1 week after 30 min of middle cerebral artery occlusion, the order of vulnerability was projection neurons > parvalbumin-expressing interneurons > nitric oxide synthase-containing interneurons > cholinergic interneurons. Within the ischemic lesion, projection neurons were almost completely lost whereas cholinergic interneurons were spared. Calretinin-immunoreactive interneurons also seemed resistant to the insult. Expression of p75(NTR) was induced in cholinergic interneurons within the lesioned area, raising the possibility of a protective action. However, the number of cholinergic interneurons was unaffected in p75(NTR) knockout mice subjected to the same ischemic insult. These quantitative data demonstrate that striatal neurons in the mouse are differentially susceptible to ischemic damage and argue against a significant role of p75(NTR) for the high resistance of cholinergic interneurons.
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| 36. |
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| 37. |
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| 38. |
- Arora, H., et al.
(författare)
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Potential role of lncRNA in impairing cellular properties of human neural progenitor cells following exposure to Zika virus E protein
- 2023
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Ingår i: Experimental Neurology. - 0014-4886. ; 368
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Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) infection during the first trimester of the pregnancy may lead to Congenital zika syndrome in the neonates. The viral infection hampers foetal brain development and causes microcephaly. Human neural progenitor cells (hNPCs) play an important role in brain development, however they are highly susceptible to ZIKV infection. In this study, we elucidated the molecular mechanisms that lead to cellular alterations in hNPCs due to ZIKV E-protein. We investigated proliferation, differentiation, migration and inflammation in hNPCs, which may lead to microcephaly. In our study, we found that ZIKV E-protein causes cell cycle arrest, decrease in proliferation and increase in mitotic length of the dividing hNPCs. We observed CyclinD1 and upstream molecules (p21 and p53) of the pathway are dysregulated, and intracellular calcium at basal level as well as upon ATP stimulation were reduced following over expression of ZIKV E-protein. ZIKV E-protein transfected hNPCs exhibited pre-mature differentiation with pro-neural genes upregulated. Furthermore, ZIKV E-protein disrupted migrational properties of hNPCs and caused elevated levels of inflammatory chemokines and cytokines. To gain insights into molecular mechanisms of these effects on hNPCs, we explored the possible involvement of long non coding RNAs in ZIKV neuropathogenesis. We have shortlisted lncRNAs associated with differentially expressed genes from publicly available transcriptomic data and found some of those lncRNAs are differentially expressed upon E-protein transfection of hNPCs. Gene ontology analysis suggest these lncRNAs play an important role in regulation of viral life cycle, host's defence response and cell proliferation.
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| 39. |
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| 40. |
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| 41. |
- Barry, Melissa, et al.
(författare)
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Utility of intracerebral theta burst electrical stimulation to attenuate interhemispheric inhibition and to promote motor recovery after cortical injury in an animal model
- 2014
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Ingår i: Experimental Neurology. - : Academic Press. - 0014-4886 .- 1090-2430. ; 261, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the injury is thought to reduce the potential for new motor learning. In part, this may be caused by an imbalance of interhemispheric inhibition (IHI); therefore, treatments that relieve the inhibitory drive from the healthy hemisphere to the peri-lesional area may enhance motor recovery. Theta burst stimulation delivered by transcranial magnetic stimulation has been tested as a means of normalizing IHI, but clinical results have been variable. Here we use a new rat model of synaptic IHI to demonstrate that electrical intracranial theta burst stimulation causes long-lasting changes in motor cortex excitability. Further, we show that contralateral intermittent theta burst stimulation (iTBS) blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that contralesional iTBS applied during recovery from cortical injury in rats improves the recovery of motor function. These findings suggest that theta burst stimulation delivered through implanted electrodes may be a promising avenue to explore for augmenting rehabilitation from brain injury.
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| 42. |
- Berg, A., et al.
(författare)
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Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3
- 2012
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 237:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- Complement proteins C1q and C3 play a critical role in synaptic elimination during development. Axotomy of spinal motoneurons triggers removal of synaptic terminals from the cell surface of motoneurons by largely unknown mechanisms. We therefore hypothesized that the complement system is involved also in synaptic stripping of injured motoneurons. In the sciatic motor pool of wild type (WT) mice, the immunoreactivity (IR) for both C1q and C3 was increased after sciatic nerve transection (SNT). Mice deficient in C3 (C3(-/-)) showed a reduced loss of synaptic terminals from injured motoneurons at one week after SNT, as assessed by immunoreactivity for synaptic markers and electron microscopy. In particular, the removal of putative inhibitory terminals, immunopositive for vesicular inhibitory amino acid transporter (VIAAT) and ultrastructurally identified as type F synapses, was reduced in C3(-/-) mice. In contrast, lesion-induced removal of nerve terminals in C1q(-/-) mice appeared similar to WT mice. Growth associated protein (GAP)-43 mRNA expression in lesioned motoneurons increased much more in C3(-/-) compared to WT mice after SNT. After sciatic nerve crush (SNC), the C3(-/-) mice showed a faster functional recovery, assessed as grip strength, compared to WT mice. No differences were detected regarding nerve inflammation at the site of injury or pattern of muscle reinnervation. These data indicate that a non-classical pathway of complement activation is involved in axotomy-induced adult synapse removal, and that its inhibition promotes functional recovery. (c) 2012 Elsevier Inc. All rights reserved.
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| 43. |
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| 44. |
- Berglöf, Elisabet, et al.
(författare)
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Locus coeruleus promotes survival of dopamine neurons in ventral mesencephalon : An in oculo grafting study
- 2009
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 216:1, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease is a neurodegenerative disorder where dopamine neurons in the substantia nigra of ventral mesencephalon undergo degeneration. In addition to the loss of dopamine neurons, noradrenaline neurons in the locus coeruleus degenerate, actually to a higher extent than the dopamine neurons. The interaction between these two nuclei is yet not fully known, hence this study was undertaken to investigate the role of locus coeruleus during development of dopamine neurons utilizing the intraocular grafting model. Fetal ventral mesencephalon and locus coeruleus were implanted either as single grafts or co-grafts, placed in direct contact or at a distance. The results revealed that the direct attachment of locus coeruleus to ventral mesencephalon enhanced graft volume and number of tyrosine hydroxylase (TH)-positive neurons in ventral mesencephalic grafts. Cell counts of subpopulations of TH-positive neurons also immunoreactive for aldehyde dehydrogenase 1-A1 (ALDH1) or calbindin, revealed improved survival of ALDH1/TH-positive neurons. However, the number of calbindin/TH-positive neurons was not affected. High density of dopamine-beta-hydroxylase (DBH)-positive innervation in the ventral mesencephalon placed adjacent to locus coeruleus was correlated to the improved survival. Ventral mesencephalic tissue, implanted at a distance to locus coeruleus, did not demonstrate improved survival, although DBH-positive nerve fibers were detected. In conclusion, the direct contact of locus coeruleus resulting in dense noradrenergic innervation of ventral mesencephalon is beneficial for the survival of ventral mesencephalic grafts. Thus, when trying to rescue dopamine neurons in Parkinson's disease, improving the noradrenergic input to the substantia nigra might be worth considering.
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- Bimpisidis, Zisis, et al.
(författare)
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Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease
- 2017
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 292, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease.
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