behavioral consequences of nmda antagonist-induced neuroapoptosis in the infant mouse brain行为的后果nmda antagonist-induced neuroapoptosis婴儿老鼠的大脑.pdfVIP

Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain 1,2 . 1. 1 2 1 Carla M. Yuede * , David F. Wozniak , Catherine E. Creeley , George T. Taylor , John W. Olney , Nuri B. Farber1. 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Department of Psychology, University of Missouri, St. Louis, Missouri, United States of America Abstract Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of e