Apoptosis in the dorsal lateral geniculate nucleus after monocular deprivation involves glutamate signaling, NO production, and PARP activation

In mammals, visual experience during early postnatal life is critical for n ormal development of the visual system. Here we report that monocular depri vation for 2, 7, and 14 consecutive days causes p53 accumulation, cell deat h, and progressive loss of neurones in the dorsal lateral geniculate nucleu s (dLGN) of newborn rats and these are prevented by NMDA and non-NMDA gluta mate receptor antagonists, and by L-NAME, an inhibitor of nitric oxide synt hesis. Monocular deprivation also increases dLGN levels of citrulline, the coproduct of nitric oxide synthesis, and this, as well as cell death and ne uronal loss, is abolished by antagonists of glutamate receptors and by L-NA ME. Finally, poly-(ADP-ribose) polymerase (PARP) knock-out mice appear to b e protected from monocular deprivation-induced cell death. In conclusion, d uring early postnatal development of the rat visual system monocular depriv ation causes excitotoxic, nitric oxide-mediated, cell death in the dLGN tha t appears to be apoptotic and also requires activation of PARP. (C) 2000 Ac ademic Press.