Mutant α-synuclein exacerbates age-related decrease of neurogenesis
- 作者：Beate Winner ; Edward Rockenstein ; D. Chichung Lie ; Robert Aigner ; Michael Mante ; Ulrich Bogdahn ; Sebastien Couillard-Despres ; Eliezer Masliah ; Jü ; rgen Winkler
- 关键词：Cell death ; Neural stem/progenitor cells ; Neurogenesis ; Olfactory bulb ; Parkinson's disease ; Synucleinopathy
- 刊名：Neurobiology of Aging
- 出版年：2008
- 期刊代码：202_01974580
- 类别：med
- 出版时间：June 2008
- 卷：29
- 期：6
- 页码：913-925
- 文件大小：4625 K
摘要
In Parkinson disease, wild-type 
-synuclein accumulates during aging, whereas -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 -synuclein. We examined the subventricular zone/olfactory bulb neurogenesis in aged mice expressing either wild-type human or A53T mutant -synuclein. Aging wild-type and mutant -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 -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 -synuclein expression and in the olfactory bulb, following wild-type and mutant -synuclein expression. The impaired neurogenesis in the olfactory bulb of different transgenic -synuclein mice during aging highlights the need to further explore the interplay between olfactory dysfunction and neurogenesis in Parkinson disease.
-synuclein accumulates during aging, whereas -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 -synuclein. We examined the subventricular zone/olfactory bulb neurogenesis in aged mice expressing either wild-type human or A53T mutant -synuclein. Aging wild-type and mutant -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 -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 -synuclein expression and in the olfactory bulb, following wild-type and mutant -synuclein expression. The impaired neurogenesis in the olfactory bulb of different transgenic -synuclein mice during aging highlights the need to further explore the interplay between olfactory dysfunction and neurogenesis in Parkinson disease.