書誌： Congenital Anomalies ,2010
Congenital Anomalies 2010; 50, 58–63
Shuichi Ueda, Kanji Yoshimoto, Taro Kadowaki, Koichi Hirata, and Shin-ichi Sakakibara
ABSTRACT Environmental enrichment (EE) facilitatesrecovery from behavioral abnormalities and spatial memorydisabilities in several neurological disease models. Exposure toEE improves spatial memory acquisition and enhances thesurvival of newly generated cells in the dentate gyri of adultrodents. However, the effects of EE on spatial learning andneurogenesis in the methylazoxymethanol acetate-inducedmicroencephalic rat have not been investigated. Depletionof serotonin in the rat hippocampus is known to influencespatial memory and adult neurogenesis, suggesting a role forserotonin in these processes. To confirm this hypothesis, malemethylazoxymethanol acetate-induced microencephalic ratswere exposed to EE or conventional housing after weaning;half of these rats further received intracisternal 5,7-dihydroxytryptamine on postnatal day 3, to induce long-lastingdepletion of serotonin. As adults, these microencephalic ratswere observed using the Morris water maze test and examinedfor hippocampal neurogenesis. EE alleviated the impairment ofspatial memory acquisition and enhanced neurogenesis in thedentate gyri of adult microencephalic rats. Injection of 5,7-dihydroxytryptamine during the neonatal period caused pronounced reductions in hippocampal serotonin levels in theserats. Long-lasting depletion of serotonin eliminated theEE-induced alleviation of spatial memory acquisition and neurogenesis impairment in microencephalic rats. The presentresults suggest that EE alleviates spatial memory performancedeficits in microencephalic rats and further indicate that serotonin might be involved in the underlying mechanisms throughincreased hippocampal neurogenesis. These data providenew insights into therapeutic interventions for individualswith human migration disorders associated with learningdisabilities.
Key Words: dentate gyrus, microencephaly, neurogenesis, serotonin, water maze