Kandasamy, Mahesh and Couillard-Despres, Sebastien and Raber, Kerstin A. and Stephan, Michael and Lehner, Bernadette and Winner, Beate and Kohl, Zacharias and Rivera, Francisco J. and Nguyen, Huu Phuc and Riess, Olaf and Bogdahn, Ulrich and Winkler, Juergen and von Horsten, Stephan and Aigner, Ludwig (2010) Stem Cell Quiescence in the Hippocampal Neurogenic Niche Is Associated With Elevated Transforming Growth Factor-beta Signaling in an Animal Model of Huntington Disease. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 69 (7). pp. 717-728. ISSN 0022-3069, 1554-6578
Full text not available from this repository. (Request a copy)Abstract
Cellular proliferation, differentiation, integration, and survival within the adult neural stem cell niche are altered under pathological conditions, but the molecular cues regulating the biology of this niche are mostly unknown. We examined the hippocampal neural stem cell niche in a transgenic rat model of Huntington disease. In this model, progressive cognitive deficits develop at the age of 9 months, suggesting possible hippocampal dysfunction. We found a disease-associated progressive decline in hippocampal progenitor cell proliferation accompanied by an expansion of the pool of 5-bromo-2-deoxyuridine labelYretaining Sox-2-positive quiescent stem cells in the transgenic animals. Increments in quiescent stem cells occurred at the expense of cAMP-responsive element-binding protein-mediated neuronal differentiation and survival. Because elevated levels of transforming growth factor-beta 1 (TGF-beta 1) impair neural progenitor proliferation, we investigated hippocampal TGF-beta signaling and determined that TGF-beta 1 induces the neural progenitors to exit the cell cycle. Although phospho-Smad2, an effector of TGF-beta signaling, is normally absent in subgranular stem cells, it accumulated progressively in Sox2/glial fibrillary acidic protein-expressing cells of the subgranular zone in the transgenic rats. These results indicate that alterations in neurogenesis in transgenic Huntington disease rats occur in successive phases that are associated with increasing TGF-beta signaling. Thus, TGF-beta 1 signaling seems to be a crucial modulator of neurogenesis in Huntington disease and may represent a target for future therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC RAT MODEL; ADULT NEURAL STEM; R6/2 MOUSE MODEL; ALZHEIMERS-DISEASE; TGF-BETA; MICE; BRAIN; GENE; Adult neurogenesis; Huntington disease; Neural stem cells; Neuronal differentiation; Proliferation; Transforming growth factor-beta |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jul 2020 11:58 |
| Last Modified: | 27 Jul 2020 11:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24519 |
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