Nucci C, Piccirilli S, Rodinò P, Nisticò R, Grandinetti M, Cerulli L, Leist M, Nicotera P, Bagetta G
Department of Biopathology, Chair of Physiopathological Optics, University of Rome "Tor Vergata", Via O. Raimondo, Rome, 00173, Italy.
Biochem Biophys Res Commun. 2000 Nov 19;278(2):360-7. doi: 10.1006/bbrc.2000.3811.
In mammals, visual experience during early postnatal life is critical for normal development of the visual system. Here we report that monocular deprivation for 2, 7, and 14 consecutive days causes p53 accumulation, cell death, and progressive loss of neurones in the dorsal lateral geniculate nucleus (dLGN) of newborn rats and these are prevented by NMDA and non-NMDA glutamate receptor antagonists, and by L-NAME, an inhibitor of nitric oxide synthesis. Monocular deprivation also increases dLGN levels of citrulline, the coproduct of nitric oxide synthesis, and this, as well as cell death and neuronal loss, is abolished by antagonists of glutamate receptors and by L-NAME. Finally, poly-(ADP-ribose) polymerase (PARP) knock-out mice appear to be protected from monocular deprivation-induced cell death. In conclusion, during early postnatal development of the rat visual system monocular deprivation causes excitotoxic, nitric oxide-mediated, cell death in the dLGN that appears to be apoptotic and also requires activation of PARP.
在哺乳动物中，出生后早期的视觉体验对于视觉系统的正常发育至关重要。在此我们报告，新生大鼠连续2天、7天和14天单眼剥夺会导致p53积累、细胞死亡以及背外侧膝状核（dLGN）中神经元的逐渐丧失，而NMDA和非NMDA谷氨酸受体拮抗剂以及一氧化氮合成抑制剂L-NAME可预防这些情况。单眼剥夺还会增加dLGN中瓜氨酸（一氧化氮合成的副产物）的水平，而谷氨酸受体拮抗剂和L-NAME可消除这种情况以及细胞死亡和神经元丧失。最后，聚（ADP-核糖）聚合酶（PARP）基因敲除小鼠似乎可免受单眼剥夺诱导的细胞死亡影响。总之，在大鼠视觉系统出生后早期发育过程中，单眼剥夺会在dLGN中导致兴奋性毒性、一氧化氮介导的细胞死亡，这种死亡似乎是凋亡性的，并且还需要PARP的激活。
