Bax, Bcl-2, and cyclin expression and apoptosis in rat substantia nigra during development

Naturally occurring cell death via apoptosis has been reported in the substantia nigra of rats during development, culminating during the perinatal period. Cellular pathways leading to apoptotic death of developing nigral dopamine neurons remain unknown, although the apoptotic mediator, caspase 3, has been shown to be activated during this process. Our previous results demonstrated the inability of antioxidants to rescue the nigral dopamine neurons that undergo apoptosis during development. In the present study, we investigated using immunohistochemistry the expression of cyclins D1, D3, and E in the substantia nigra during pre- and postnatal development, since their re-expression in postmitotic neurons has been proposed to contribute to developmental apoptosis. We also investigated by Western blot analysis of nigral tissue isolated during the first postnatal week the expression of the anti- and pro-apoptotic proteins, Bcl-2 and Pax, respectively, since altered Bcl-2 expression during developmental apoptosis has been described. During apoptotic death of nigral dopamine neurons in development, we detected a significant increase in the Bax:Bcl-2 ratio, which is consistent with enhanced apoptosis. There were no changes in the expression of the cyclins during the same apoptotic period. These novel findings suggest that nigral dopamine neurons undergo developmental apoptotic death through a Bax:Bcl-2-sensitive pathway that does not involve cyclin mediation. (C) 2001 Published by Elsevier Science Ireland Ltd.