Complex-environment rearing prevents prenatal hypoxia-induced deficits in hippocampal cellular mechanisms necessary for memory consolidation in the adult Wistar rat.
Hypoxic episodes in utero can result in enduring and debilitating neurological sequelae that include nonprogressive motor disorders and/or significant learning deficits. The extent of long-term disruption of synaptic function following prenatal hypoxia and its subsequent effect on learning ability, however, remain to be established. Polysialylation of the neural cell adhesion molecule, a cellular event integral to the consolidation of diverse learning paradigms, was used to correlate cellular end points with learning deficits as a consequence of prenatal hypoxia. Pregnant Wistar dams exposed to hypobaric hypoxia during gestational days 10-20 had significantly reduced litter sizes, but the lack of effect on subsequent pup weight gain suggested no gross developmental deficit. By contrast, adult animals with prior in utero hypoxia exhibited significant learning difficulties in both acquisition of a water maze spatial learning task and recall of a passive avoidance paradigm. Learning deficits correlated with a significant reduction in the frequency of polysialylated neurons in the dentate infragranular zone and a blunting of their transient activation 12 hr following task acquisition. Rearing animals with prior prenatal hypoxia in a complex environment, however, eliminated the task acquisition and recall deficits and restored dentate polysialylated cell frequency and their transient posttraining increase.
Foley
Andrew G
AG
Department of Pharmacology, The Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Murphy
Keith J
KJ
Regan
Ciaran M
CM
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004780:Environment, Controlled; D005260:Female; D005311:Fetal Hypoxia / Q000473:pathology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis; D009434:Neural Pathways / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000096:biosynthesis
D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule