non-injurious neonatal hypoxia confers resistance to brain senescence in aged male ratsnon-injurious新生儿缺氧抵抗衰老的雄性老鼠的脑衰老.pdfVIP

Non-Injurious Neonatal Hypoxia Confers Resistance to Brain Senescence in Aged Male Rats 1,2 ´ 1,2 1,2 1,2 1,2 Nicolas Martin , Carine Bossenmeyer-Pourie , Violette Koziel , Rozat Jazi , Sandra Audonnet , 3 ´ 1,2,4 1,2. ´ ´ 1,2 . Paul Vert , Jean-Louis Gueant , Jean-Luc Daval , Gregory Pourie * ` ´ ´ ´ ` ´ ´ ´ 1 Inserm U954, Vandoeuvre-les-Nancy, France, 2 Universite de Lorraine, Faculte de Medecine, Vandoeuvre-les-Nancy, France, 3 Service de Medecine Neonatale, Maternite ´ Regionale Universitaire, Nancy, France, 4 IRCCS, Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy Abstract Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal ‘‘conditioning-like’’ hypoxia (100% N2, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase. At 21 days of age, increased thicknesse