Stem cell quiescence in the hippocampal neurogenic niche is associated with elevated transforming growth factor-β signaling in an animal model of huntington disease

Kandasamy M, Couillard-Despres S, Raber KA, Stephan M, Lehner B, Winner B, Kohl Z, Rivera FJ, Nguyen HP, Riess O, Bogdahn U, Winkler J, Von Hörsten S, Aigner L (2010)

Publication Type: Journal article

Publication year: 2010

Journal

Journal of Neuropathology and Experimental Neurology Oxford University Press

Book Volume: 69

Pages Range: 717-728

Journal Issue: 7

DOI: 10.1097/NEN.0b013e3181e4f733

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 9months, 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 label-retaining 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-β1 (TGF-β1) impair neural progenitor proliferation, we investigated hippocampal TGF-β signaling and determined that TGF-β1 induces the neural progenitors to exit the cell cycle. Although phospho-Smad2, an effector of TGF-β 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-β signaling. Thus, TGF-β1 signaling seems to be a crucial modulator of neurogenesis in Huntington disease and may represent a target for future therapy. © 2010 by the American Association of Neuropathologists, Inc.

Authors with CRIS profile

Zacharias Kohl Department of Molecular Neurology Jürgen Winkler Professur für Molekulare Neurologie

Involved external institutions

Paracelsus Medizinische Privatuniversität AT Austria (AT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Kandasamy, M., Couillard-Despres, S., Raber, K.A., Stephan, M., Lehner, B., Winner, B.,... Aigner, L. (2010). Stem cell quiescence in the hippocampal neurogenic niche is associated with elevated transforming growth factor-β signaling in an animal model of huntington disease. Journal of Neuropathology and Experimental Neurology, 69(7), 717-728. https://doi.org/10.1097/NEN.0b013e3181e4f733

MLA:

Kandasamy, Mahesh, et al. "Stem cell quiescence in the hippocampal neurogenic niche is associated with elevated transforming growth factor-β signaling in an animal model of huntington disease." Journal of Neuropathology and Experimental Neurology 69.7 (2010): 717-728.

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