title: Mutant alpha-synuclein exacerbates age-related decrease of neurogenesis.
abstract: 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.
authors.affiliation: Department of Neurology, University of Regensburg, Universitaetsstr. 84, 93053 Regensburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: D Chichung
authors.initials: DC
authors.lastname: Lie
authors.forename: Robert
authors.initials: R
authors.lastname: Aigner
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Sebastien
authors.initials: S
authors.lastname: Couillard-Despres
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009830:Olfactory Bulb / Q000254:growth & development*; D010300:Parkinson Disease / Q000503:physiopathology; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein