Mutant α-synuclein exacerbates age-related decrease of neurogenesis

NEUROBIOLOGY OF AGING

卷:29

Article

Winner, Beate¹  Rockenstein, Edward²  Lie, D. Chichung³  Aigner, Robert¹  Mante, Michael²  Bogdahn, Ulrich¹  Couillard-Despres, Sebastien¹  Masliah, Eliezer²  Winkler, Juergen^1,2 

[1] Univ Regensburg, Dept Neurol, D-93053 Regensburg, Germany

[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[3] GSF Natl Res Ctr Environm & Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany

关键词: cell death;    neural stem/progenitor cells;    neurogenesis;    olfactory bulb;    Parkinson's disease;    synucleinopathy;   

DOI  :  10.1016/j.neurobiolaging.2006.12.016

来源: Elsevier

【 摘 要 】

In Parkinson disease, wild-type alpha-synuclein accumulates during aging, whereas alpha-synuclein mutations lead to an early onset and accelerated course of the disease. The generation of new neurons is decreased in regions of neurogenesis in adult mice overexpressing wild-type human alpha-synuclein. We examined the subventricular zone/olfactory bulb neurogenesis in aged mice expressing either wild-type human or A53T mutant alpha-synuclein. Aging wild-type and mutant alpha-synuclein-expressing animals generated significantly fewer new neurons than their non-transgenic littermates. This decreased neurogenesis was caused by a reduction in cell proliferation within the subventricular zone of mutant alpha-synuclein mice. In contrast, no difference was detected in mice overexpressing the wild-type allele. Also, more TUNEL-positive profiles were detected in the subventricular zone, following mutant alpha-synuclein expression and in the olfactory bulb, following wild-type and mutant alpha-synuclein expression. The impaired neurogenesis in the olfactory bulb of different transgenic alpha-synuclein mice during aging highlights the need to further explore the interplay between olfactory dysfunction and neurogenesis in Parkinson disease. (C) 2007 Elsevier Inc. All rights reserved.

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