| 1. |
- Brännvall, Karin, et al.
(author)
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Central nervous system stem/progenitor cells form neurons and peripheral glia after transplantation to the dorsal root ganglion.
- 2006
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In: NeuroReport. - 0959-4965 .- 1473-558X. ; 17:6, s. 623-628
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Journal article (peer-reviewed)abstract
- We asked whether neural stem/progenitor cells from the cerebral cortex of E14.5 enhanced green fluorescent protein transgenic mice are able to survive grafting and differentiate in the adult rat dorsal root ganglion. Neurospheres were placed in lumbar dorsal root ganglion cavities after removal of the dorsal root ganglia. Alternatively, dissociated neurospheres were injected into intact dorsal root ganglia. Enhanced green fluorescent protein-positive cells in the dorsal root ganglion cavity were located in clusters and expressed beta-III-tubulin or glial fibrillary acidic protein after 1 month, whereas after 3 months, surviving grafted cells expressed only glial fibrillary acidic protein. In the intact adult DRG, transplanted neural stem/progenitor cells surrounded dorsal root ganglion cells and fibers, and expressed glial but not neuronal markers. These findings show that central nervous system stem/progenitor cells can survive and differentiate into neurons and peripheral glia after xenotransplantation to the adult dorsal root ganglion.
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| 2. |
- Goursaud, Stephanie, et al.
(author)
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Cultured astrocytes derived from corpus callosum or cortical grey matter show distinct glutamate handling properties
- 2009
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 108:6, s. 1442-1452
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Journal article (peer-reviewed)abstract
- While the astrocytic control of extracellular glutamate concentration at synaptic contacts is well characterized, little is known regarding the clearance of glutamate along axon tracts, even though local excitotoxic damage has been reported. Therefore, we have compared glutamate handling in astrocyte cultures derived from white matter (corpus callosum) and grey matter tissues (cortical structures). These populations of astrocytes showed clearly distinct phenotypes, adopting stellate or protoplasmic morphologies respectively. In addition, white matter astrocytes showed high densities of the intermediate filament proteins glial fibrillary acidic protein, vimentin and nestin. The glutamate-aspartate transporter and glutamate transporter-1, as well as glutamine synthetase, were found to be expressed at higher levels in white matter compared with grey matter astrocytes. Consistent with this aspartate uptake capacity was three to fourfold higher in white matter cells, and the use of specific inhibitors revealed a substantial activity of glutamate transporter-1, contrasting with grey matter cells where this transporter appeared poorly functional. In addition, expression of type 5 metabotropic glutamate receptors was considerably higher in white matter astrocytes where the agonist (S)-3,5-dihydroxyphenylglycine triggered a large release of intracellular calcium. Differences in these astrocyte cultures were also observed when exposed to experimental conditions that trigger glial activation. This study highlights typical features of cultured astrocytes derived from white matter tissues, which appear constitutively adapted to handle excitotoxic insults. Moreover, the expression and activity of the astroglial components involved in the control of glutamatergic transmission are reinforced when these cells are maintained under conditions mimicking a gliotic environment.
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| 3. |
- Hanna-Mitchell, Ann T, et al.
(author)
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The impact of neurotrophin-3 on the dorsal root transitional zone following injury
- 2008
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In: Spinal Cord. - 1362-4393 .- 1476-5624. ; 46:12, s. 804-810
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Journal article (peer-reviewed)abstract
- Study design: Morphological and Stereological assessment of the dorsal root transitional zone (DRTZ) following complete crush injury, using light microscopy (LM) and transmission electron microscopy (TEM).Objectives: To assess the effect of exogenous neurotrophin-3 (NT-3) on the response of glial cells and axons to dorsal root damage.Setting: Department of Anatomy, University College Cork, Ireland and Department of Physiology, UMDS, University of London, UK.Methods: Cervical roots (C6-8) from rats which had undergone dorsal root crush axotomy 1 week earlier, in the presence (n = 3) and absence (n = 3) of NT-3, were processed for LM and TEM.Results: Unmyelinated axon number and size was greater in the DRTZ proximal ( Central Nervous System; CNS) and distal ( Peripheral Nervous System; PNS) compartments of NT-3-treated tissue. NT-3 was associated with a reduced astrocytic response, an increase in the proportion of oligodendrocytic tissue and a possible inhibition or delay of microglial activation. Disrupted-myelin volume in the DRTZ PNS and CNS compartments of treated tissue was lower, than in control tissue. In the PNS compartment, NT-3 treatment increased phagocyte and blood vessel numbers. It decreased myelinating activity, as sheath thickness was significantly lower and may also account for the noted lower Schwann cell and organelle volume in the test group.Conclusions: Our observations suggest that NT-3 interacts with non-neuronal tissue to facilitate the regenerative effort of damaged axons. This may be as a consequence of a direct action or indirectly mediated by modulation of non-neuronal responses to injury.
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| 4. |
- Kozlova, Elena N., 1956-, et al.
(author)
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Differentiation and migration of neural crest stem cells are stimulated by pancreatic islets
- 2009
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In: NeuroReport. - 0959-4965 .- 1473-558X. ; 20:9, s. 833-838
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Journal article (peer-reviewed)abstract
- Neural crest stem cells (NCSCs) migrate during embryonic development towards the endoderm-derived pancreas and the interaction between NCSCs and beta-cellprogenitors is crucial for their mutual differentiation. In diabetes, loss ofbeta-cells or impaired beta-cell function is accompanied by nerve degeneration,which contributes to the progression of the disease. Here we show that adultpancreatic islets markedly promote differentiation of NCSCs towards neuronalphenotype in vitro and in vivo after transplantation and increase their migrationtowards islets. These findings indicate that pancreatic islets can be used topromote differentiation of NCSCs towards neuronal phenotype and that thisin-vitro system may help elucidate interactions between NCSCs and healthy ordiseased beta-cells.
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| 5. |
- Takenaga, Keizo, et al.
(author)
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Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo
- 2007
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 25:3, s. 455-463
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Journal article (peer-reviewed)abstract
- The calcium-binding Mtsl/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration ofC6 cells on astrocytes, using short interference (si) RNA to silence Mtsl/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mtsl/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern ofC6 cells is affected by their intrinsic Mtsl/S100A4 expression as well as Mtsl/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mtsl in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mtsl than low-grade astrocytic tumors.
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| 6. |
- Åkesson, Elisabet, et al.
(author)
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Long-term survival, robust neuronal differentiation, and extensive migration of human forebrain stem/progenitor cells transplanted to the adult rat dorsal root ganglion cavity
- 2008
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In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 17:10-11, s. 1115-1123
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Journal article (peer-reviewed)abstract
- Neurons in dorsal root ganglia (DRGs) transmit sensory information from peripheral tissues to the spinal cord. This pathway can be interrupted, for example, as the result of physical violence, traffic accidents, or complications during child delivery. As a consequence, the patient permanently loses sensation and often develops intractable neuropathic pain in the denervated area. Here we investigate whether human neural stem/progenitor cells (hNSPCs) transplanted to the DRG cavity can serve as a source for repairing lost peripheral sensory connections. We found that hNSPCs robustly differentiate to neurons, which survive long-term transplantation. The neuronal population in the transplants was tightly surrounded by astrocytes, suggesting their active role in neuron survival. Furthermore, 3 months after grafting hNSPCs were found in the dorsal root transitional zone (DRTZ) and within the spinal cord. The level of differentiation of transplanted cells was high in the core of the transplants whereas cells that migrated to the DRTZ and spinal cord were undifferentiated, nestin-expressing precursors. These data indicate that peripherally transplanted hNPSCs can be used for repair of dorsal root avulsion or spinal cord injuries; however, additional factors are required to guide their differentiation to the desired type of neurons. Furthermore, hNPSCs that migrate from the DRG cavity graft site to the DRTZ and spinal cord may provide trophic support for regenerating dorsal root axons, thereby allowing them to reenter the host spinal cord.
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