Expression of Cell Death‐Associated Proteins in Neuronal Apoptosis Associated with Pontosubicular Neuron Necrosis

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Abstract
Expression of apoptosis‐associated proteins p53, bcl‐2, bax, and caspase‐3/CPP32, activation of caspase‐3, and modification of proteins via poly(ADP‐ribosyl)ation was studied in pontosubicular neuron necrosis (PSN), a form of perinatal brain damage revealing the morphological hallmarks of neuronal apoptosis. Immunoreactivity for p53 was completely absent. The majority of cells stained with the bax and procaspase‐3 antibodies did not show morphological signs of apoptosis. In contrast, an antibody against activated caspase‐3 almost exclusively stained cells with apoptotic morphology. Poly(ADP‐ribosyl)ated proteins were only rarely detected in cells with apoptotic morphology. The expression patterns of bax, procaspase‐3, bcl‐2, and p53 in PSN were similar to that found in age‐matched control brains. However, activated caspase‐3 and poly‐ADP‐ribosylated proteins were exclusively found in apoptotic cells. These data indicate that detection of active caspase‐3 is a reliable marker for apoptosis in formalin‐fixed human tissue, and that neuronal apoptosis in pontosubicular neuron necrosis is accompanied by a pronounced activation of caspase‐3.
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