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 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.
Nucci
C
C
Department of Biopathology, Chair of Physiopathological Optics, University of Rome "Tor Vergata", Via O. Raimondo, Rome, 00173, Italy.
Piccirilli
S
S
Rodinò
P
P
Nisticò
R
R
Grandinetti
M
M
Cerulli
L
L
Leist
M
M
Nicotera
P
P
Bagetta
G
G
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D004789:Enzyme Activation; D005829:Geniculate Bodies / Q000166:cytology* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction
D017470:Receptors, Glutamate; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D011065:Poly(ADP-ribose) Polymerases