Possibility for neurogenesis in substantia nigra of parkinsonian brain

Kenji Yoshimi, Yong Ri Ren, Tatsunori Seki, Masanori Yamada, Hideki Ooizumi, Masafumi Onodera, Yuko Saito, Shigeo Murayama, Hideyuki Okano, Yoshikuni Mizuno, Hideki Mochizuki

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalAnnals of Neurology
Issue number1
Publication statusPublished - 2005 Jul

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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