Mutant α‐synuclein and aging reduce neurogenesis in the acute 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine model of Parkinson’s disease

Aging Cell

Jun Peng¹ 

[1] Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA

关键词: Aging;    Parkinson’s disease;    proliferation;    progenitor;    substantia nigra;    α‐synuclein;   

DOI  :  10.1111/j.1474-9726.2010.00656.x

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland