Open AccessMutant α‐synuclein and aging reduce neurogenesis in the acute 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine model of Parkinson’s disease
Author(s) -
Peng Jun,
Andersen Julie K.
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00656.x
Subject(s) - neurogenesis , mptp , substantia nigra , subventricular zone , biology , subgranular zone , dentate gyrus , olfactory bulb , neuroscience , neural stem cell , hippocampal formation , endocrinology , medicine , microbiology and biotechnology , stem cell , dopaminergic , central nervous system , dopamine
Summary Neurogenesis, the production of new neurons from less differentiated precursor cells, normally occurs in adult brains in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. Neurogenesis declines with aging. In previous studies, neurogenesis was stimulated by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride (MPTP) in young animals. In this study, we examined the effect of acute MPTP administration and mutant α‐synuclein A53T on neurogenesis and migration of newborn neurons in the aged (23‐month) vs. young (2‐month) rodent brain. Cell proliferation and neurogenesis were assessed via bromodeoxyuridine labeling and immunostaining for cell type‐specific markers. In the aged brain, neural precursor cells in the rostral SVZ retained the capacity for proliferation and migration in response to MPTP‐induced Parkinsonism, although the response is less robust than in younger animals. Furthermore, in transgenic mice that overexpress mutant α‐synuclein (A53T), brains examined day 21 after MPTP administration showed markedly decreased olfactory bulb and substantia nigra neurogenesis. Our data suggest that in addition to aging effects associated with decline in the number of newly generated cells, mutant α‐synuclein reduces MPTP‐induced neurogenesis. This could provide a novel therapeutic target for chronic brain repair in this condition.