Short hypoxia could attenuate the adverse effects of hyperhomocysteinemia on the developing rat brain by inducing neurogenesis.
Gestational deficiency in methyl donors such as folate and vitamin B12 impairs homocysteine metabolism and can alter brain development in the progeny. Since short hypoxia has been shown to be neuroprotective in preconditioning studies, we aimed to investigate the effects of brief, non-lesioning neonatal hypoxia (100% N2 for 5 min) on the developing brain of rats born to dams fed either a standard diet or a diet lacking vitamins B12, B2, folate and choline until offspring's weaning. While having no influence on brain accumulation of homocysteine and concomitant apoptosis in 21-day-old deficient pups, exposure to hypoxia reduced morphological injury of the hippocampal CA1 layer. It also markedly stimulated the incorporation of bromodeoxyuridine (BrdU) in permissive areas such as the subventricular zone and the hippocampus followed by the migration of new neurons. Scores in a locomotor coordination test (days 19-21) and learning and memory behavior in the eight-arm maze (days 80-84) were found to be significantly improved in rats exposed to hypoxia in addition to the deficient diet. Therefore, by stimulating neurogenesis in rat pups, brief neonatal hypoxia appeared to attenuate the long-term effects of early exposure to a deficiency in nutritional determinants of hyperhomocysteinemia.
Blaise
Sébastien A
SA
INSERM U724, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.
Nédélec
Emmanuelle
E
Alberto
Jean-Marc
JM
Schroeder
Henri
H
Audonnet
Sandra
S
Bossenmeyer-Pourié
Carine
C
Guéant
Jean-Louis
JL
Daval
Jean-Luc
JL
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D015687:Cell Hypoxia; D019610:Cytoprotection / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D020138:Hyperhomocysteinemia / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D008607:Intellectual Disability / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018782:Maze Learning / Q000502:physiology; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014804:Vitamin B Deficiency / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy