Possibility for neurogenesis in substantia nigra of parkinsonian brain.
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.
Yoshimi
Kenji
K
Research Institute for Diseases of Old Ages, Juntendo University, Bunkyo-ku, Tokyo, Japan.
Ren
Yong-Ri
YR
Seki
Tatsunori
T
Yamada
Masanori
M
Ooizumi
Hideki
H
Onodera
Masafumi
M
Saito
Yuko
Y
Murayama
Shigeo
S
Okano
Hideyuki
H
Mizuno
Yoshikuni
Y
Mochizuki
Hideki
H
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008251:Macaca; D008297:Male; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
D012794:Sialic Acids; C021319:polysialic acid; D049452:Green Fluorescent Proteins