Endothelin B receptor deficiency is associated with an increased rate of neuronal apoptosis in the dentate gyrus

The dentate gyrus retains neuronal proliferative potential throughout life. Using immature endothelin B receptor deficient (sl/sl) rats, a rabbit mode l of pneumococcal meningitis and autopsy brains from humans who died from p neumococcal meningitis, we explored the role of endothelin B receptors in p hysiological and pathological neuronal apoptosis in the dentate gyrus. At p ostnatal days 3-4, the rate of apoptosis in the dentate gyrus was high in a ll rats, declining to low levels in wild-type rats (+/+) on days 14 and 22, but remaining high in both homozygous (sl/sl) and heterozygous (sl/+) endo thelin B receptor-deficient rats. Increased apoptosis was not significantly compensated for by neuronal proliferation. Hippocampal neuronal cultures a lso exhibited genotype-dependent apoptosis with the highest rare in neurons from homozygous endothelin B receptor-deficient (sl/sl) rats. In rabbit an d human pneumococcal meningitis, increased apoptosis in the dentate gyrus w as associated with loss of neuronal endothelin B receptor immunoreactivity. In conclusion, endothelin B receptors appear to act as neuronal survival fa ctors in the dentate gyrus in rodents and man, both during postnatal develo pment and under pathological conditions. (C) 1999 IBRO, Published by Elsevi er Science Ltd.