Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum

Apoptosis occurs not only in mitotic cells but also in postmitotic neuronal cells. We previously suggested that the tumor suppressor gene p53 is requi red for DNA strand break-induced apoptosis in dissociated culture of cerebe llar granule neurons. In this study, we examined the role of p53 in apoptos is using organotypic slice culture of cerebellum from p53 null and wild-typ e mice. Exposure to bleomycin significantly increased the numbers of TUNEL- , p53-, and c-Jun-positive neurons in the wild-type mouse cerebellar intern al granular layer (IGL) and Purkinje cell layer (PL), However, in p53-defic ient mice, these responses were not observed, These results are consistent with our previous observations in dissociated neuronal culture showing that the amount of c-Jun protein increases significantly after addition of bleo mycin in p53 wild-type cerebellar granule cells. The results presented here also indicate that p53 is involved in DNA strand break-induced apoptosis o f fully postmitotic central nervous system neurons and suggest that c-Jun e xpression occurs downstream of p53 expression. (C) 2000 Wiley-Liss, Inc.