Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery.
The impact of hypoxia in utero during delivery was correlated with the immunocytochemistry, expression and activity of the neuronal (nNOS) and inducible (iNOS) isoforms of the nitric oxide synthase enzyme as well as with the reactivity and expression of nitrotyrosine as a marker of protein nitration during early postnatal development of the cortex. The expression of nNOS in both normal and hypoxic animals increased during the first few postnatal days, reaching a peak at day P5, but a higher expression was consistently found in hypoxic brain. This expression decreased progressively from P7 to P20, but was more prominent in the hypoxic group. Immunoreactivity for iNOS was also higher in the cortex of the hypoxic rats and was more evident between days P0 and P5, decreasing dramatically between P10 and P20 in both groups of rats. Two nitrated proteins of 52 and 38 kDa, were also identified. Nitration of the 52-kDa protein was more intense in the hypoxic animals than in the controls, increasing from P0 to P7 and then decreasing progressively to P20. The 38-kDa nitrated protein was seen only from P10 to P20, and its expression was more intense in control than in the hypoxic group. These results suggest that the NO system may be involved in neuronal maturation and cortical plasticity over postnatal development. Overproduction of NO in the brain of hypoxic animals may constitute an effort to re-establish normal blood flow and may also trigger a cascade of free-radical reactions, leading to modifications in the cortical plasticity.
Fernández
Ana Patricia
AP
Neuroanatomy and Cell Biology Department, Instituto Cajal (CSIC), Avenida del Doctor Arce 37, 28002, Madrid, Spain.
Alonso
David
D
Lisazoaín
Ignacio
I
Serrano
Julia
J
Leza
Juan Carlos
JC
Bentura
María Luisa
ML
López
Juan Carlos
JC
Manuel Encinas
Juan
J
Fernández-Vizarra
Paula
P
Castro-Blanco
Susana
S
Martínez
Alfredo
A
Martinez-Murillo
Ricardo
R
Lorenzo
Pedro
P
Pedrosa
Juan Angel
JA
Peinado
María Angeles
MA
Rodrigo
José
J
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism* / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000254:growth & development* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007231:Infant, Newborn; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000201:enzymology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D005609:Free Radicals; D009566:Nitrates; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase