Reduced adult neurogenesis and neuronal abnormalities in the hippocampus underlie cognitive deficiency following prenatal administration of the anti-epileptic drug valproic acid

Prenatal exposure to valproic acid, an established anti-epileptic drug, has been reported to impair postnatal cognitive function of children from epileptic mothers. Nevertheless, its pathology and proper treatment to minimize the effects remain unknown. In mice, we found that the postnatal cognitive function impairment was mainly caused by a reduction of adult neurogenesis and abnormal neuronal features in the hippocampus, which could be ameliorated by voluntary running. Pregnant mice received an oral administration of methylcellulose (MC), valproic acid (VPA) or valpromide (VPM) once a day on three consecutive embryonic days (E) 12.5, E13.5, and E14.5 and were sampled 3hr after the last administration (E14.5), at E18.5, and at 12 weeks of age.