Altered spatial learning, cortical plasticity and hippocampal anatomy in a neurodevelopmental model of schizophrenia-related endophenotypes

摘要: Adult rats exposed to the DNA-methylating agent methylazoxymethanol on embryonic day 17 show a pattern of neurobiological deficits that model some neuropathological and behavioral changes observed in schizophrenia. Although it is generally assumed these reflect targeted disruption neurogenesis, unknown whether effects generalize other antimitotic agents administered at different stages development. In present study, neurochemical, electrophysiological techniques were used determine exposure Ara-C later development recapitulates (MAM)-treated animals patients with Male (30 mg/kg/day) days 19.5 20.5 reduced cell numbers heterotopias hippocampal CA1 CA2/3 regions, respectively, as well loss superficial layers pre- infralimbic cortex. Birth date labeling bromodeoxyuridine reveals cytoarchitectural are consequence rather direct result disrupted cortical neurogenesis. Ara-C-treated possess elevated levels dopamine DOPAC (3,4-didyhydroxypheylacetic acid) but no change norepinephrine or serotonin. impaired their ability learn Morris Water Maze task showed diminished synaptic plasticity hippocampocortical pathway. These data indicate neurogenesis constitutes useful for comparative study gestational models relationship cognitive