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  • Clarke, D J, et al. (författare)
  • Synaptic connections formed by grafts of different types of cholinergic neurons in the host hippocampus
  • 1990
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 107:1, s. 11-22
  • 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)
  • Dahlin, L B, et al. (författare)
  • Axonal growth in mesothelial chambers : effects of a proximal preconditioning lesion and/or predegeneration of the distal nerve stump
  • 1988
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 99:3, s. 63-655
  • 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.
  • Danielsen, N, et al. (författare)
  • Experimental hyperthyroidism stimulates axonal growth in mesothelial chambers
  • 1986
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 94:1, s. 54-65
  • 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.
  • Doering, L C, et al. (författare)
  • Abnormal perikaryal immunoreactivity to the phosphorylated heavy neurofilament unit in intracerebral basal forebrain transplants
  • 1991
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 111:1, s. 1-8
  • 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.
  • Ekström, Peter, et al. (författare)
  • A morphometric study of age-related changes in serotonin-immunoreactive cell groups in the brain of the coho salmon, Oncorhynchus kisutch walbaum
  • 1992
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 116:2, s. 204-209
  • 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.
  • Eriksson Linsmeier, Cecilia, et al. (författare)
  • Neuronal differentiation following transplantation of expanded mouse neurosphere cultures derived from different embryonic forebrain regions.
  • 2003
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 184:2, s. 615-635
  • 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.
  • Grabowski, Martin, et al. (författare)
  • 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
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 116:2, s. 105-121
  • 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.
  • Grover, A, et al. (författare)
  • A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
  • 2003
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 184:1, s. 131-140
  • 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.
  • Lindvall-Axelsson, Maria, et al. (författare)
  • Inhibition of cerebrospinal fluid formation by omeprazole
  • 1992
  • Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886. ; 115:3, s. 394-399
  • 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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