抄録
1-Methyl-4-Phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment has been well demonstrated to cause selective degeneration of dopaminergic neurons in the substantia nigra (SN) in the adult mouse brain in the manner similar to that seen in Parkinson’ disease. The subventricular zone (SVZ) harbors neural stem cells that retain the capacity to generate multiple cell types even in the adult. The SVZ is composed of migrating neuroblasts (A cells), astrocytes (neural stem cells, B cells), immature precursors (transit amplifying cells, C cells) and ependymal cells. Here, we demonstrated that MPTP induced apoptosis in SVZ and rostral migratory stream (RMS) in the adult C57BL/6 mouse brain.
The number of TUNEL-positive cells peaked at 24 h after MPTP injection, and decreased thereafter, paralleling the change in the number of cleaved caspase-3-positive cells in the SVZ and RMS. Results of immunohistochemistry and ultrastructural analyses indicated that the majority of apoptotic cells were A cells, while a few were B 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 paralleled the MPTP-induced apoptosis. The present results may raise a question: which are more vulnerable to MPTP toxicity, dopaminergic neurons in SN or migrating neuroblasts in SVZ and RMS? If the latter, decreased regeneration of dopaminergic neurons from SVZ neuroblasts may be crucial to the induction of MPTP Parkinsonism, in addition to the direct injury to the SN neurons.
