Methylazoximethanol acetate-induced cell death in the granule cell layer of the developing mouse cerebellum is associated with caspase-3 activation, but does not depend on the tissue-type plasminogen activator

Methylazoximethanol (MAM) acetate-induced cell death in the external granul e cell layer of the developing cerebellum affects clusters of cells with mo rphological features of apoptosis. This is accompanied by selective inducti on of active caspase-3 expression and increased c-Jun/AP-1 (N) immunoreacti vity in dying cells, as revealed with immunohistochemistry. Since the antib ody to cJun/AP-1 (N) cross-reacts with epitopes emerging after caspase-medi ated proteolysis during apoptosis, these results indicate that MAM-induced cell death is associated with active caspase-3 expression and function in d ying cells. In order to investigate the involvement of tissue-type plasmino gen activator (tPA), which has been implicated in certain forms of neuronal cell death, MAM-induced cell death has been examined in tPA(-/-) and tPA(/+) mice. No differences in the number of dying cells, as seen with haemato xylin and eosin staining and in situ end-labelling of fragmented nuclear DN A-processed sections, were seen between tPA-/- and tPA(+/+) mice. These res ults indicate that tPA is not involved in MAM-induced cell death in the dev eloping brain. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.