Mutant alpha-synuclein exacerbates age-related decrease of neurogenesis.
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.
Winner
Beate
B
Department of Neurology, University of Regensburg, Universitaetsstr. 84, 93053 Regensburg, Germany.
Rockenstein
Edward
E
Lie
D Chichung
DC
Aigner
Robert
R
Mante
Michael
M
Bogdahn
Ulrich
U
Couillard-Despres
Sebastien
S
Masliah
Eliezer
E
Winkler
Jürgen
J
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*
D051844:alpha-Synuclein