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Possibility for neurogenesis in substantia nigra of parkinsonian brain
Author(s) -
Yoshimi Kenji,
Ren YongRi,
Seki Tatsunori,
Yamada Masanori,
Ooizumi Hideki,
Onodera Masafumi,
Saito Yuko,
Murayama Shigeo,
Okano Hideyuki,
Mizuno Yoshikuni,
Mochizuki Hideki
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20506
Subject(s) - substantia nigra , neurogenesis , tyrosine hydroxylase , biology , dopamine , neural stem cell , neuroscience , pathology , stem cell , microbiology and biotechnology , medicine , dopaminergic
Recent studies of enhanced hippocampal neurogenesis by antidepressants suggest enhancement of neurogenesis is a potentially effective therapy in neurodegenerative diseases. In this study, we evaluated nigral neurogenesis in animals and autopsy brains including patients with Parkinson's disease (PD). First, proliferating cells in substantia nigra were labeled with retroviral transduction of green fluorescent protein, which is an efficient method to label neuronal stem cells. Subsequent differentiation of labeled cells was followed; many transduced cells became microglia, but no differentiation into tyrosine hydroxylase–positive neurons was detected at 4 weeks after injection, in both intact rodents and those treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine. Second, polysialic acid (PSA)–like immunoreactivity, indicative of newly differentiated neurons, was detected in the substantia nigra of rodent, primate, and human midbrains. A large number of PSA‐positive cells were detected in the substantia nigra pars reticulata of some patients with PD. In rats and a macaque monkey, the dopamine‐depleted hemispheres showed more PSA staining than the intact side. A small number of tyrosine hydroxylase–positive cells were PSA‐positive. Our results suggest enhanced neural reconstruction in PD, which may be important in the design of new therapies against the progression of PD. Ann Neurol 2005