Evidence of apoptosis in the subventricular zone and rostral migratory stream in the MPTP mouse model of Parkinson disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to create animal models of Parkinson disease. There is conflicting evidence on the occurrence of apoptosis induced by MPTP in the mouse substantia nigra pars compacta. We demonstrated that a single acute injection of MPTP induced apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) in the adult C57BL/6 mouse brain. The number of TUNEL-positive cells peaked at 24 hours after injection and decreased thereafter, paralleling the change in the number of cleaved caspase-3-positive cells after MPTP injection. Results of immunohistochemistry and ultrastructural analyses indicated that the majority of apoptotic cells in the SVZ and RMS were migrating neuroblasts (type A cells), whereas a few were astrocytes (type B cells). No apoptosis occurred in transit-amplifying progenitors (type C cells). The decrease in A cell numbers was most marked on day 2 and lasted to day 8 after the administration. A rapid and transient phagocytosis of apoptotic cells by microglial cells was demonstrated to parallel the MPTP-induced apoptosis. The present findings provide new insight into the extensive neurotoxicity of MPTP and may be valuable in reevaluating the MPTP mouse model of Parkinson disease.
He
Xi Jun
XJ
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. aaa37172@mail.goo.ne.jp
Nakayama
Hiroyuki
H
Dong
Mei
M
Yamauchi
Hirofumi
H
Ueno
Masaki
M
Uetsuka
Koji
K
Doi
Kunio
K
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000493:pharmacokinetics*; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology*; D013997:Time Factors
D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases