Fortier Marie-Eve, Joober Ridha, Luheshi Giamal N, Boksa Patricia
Department of Psychiatry and Neurology, McGill University, Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Verdun, Quebec, Canada H4H 1R3.
J Psychiatr Res. 2004 May-Jun;38(3):335-45. doi: 10.1016/j.jpsychires.2003.10.001.
An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at adulthood. The study also tested if postnatal anoxia interacted with gestational LPS exposure to affect behavior. At adulthood, offspring from dams administered LPS on days 18 and 19 of pregnancy showed significantly increased amphetamine-induced locomotion, compared to offspring from saline-treated dams. A period of anoxia on postnatal day 7 had no effect on amphetamine-induced locomotion and there was no interaction between effects of gestational LPS and postnatal anoxia on this behavior. Offspring from LPS-treated dams also showed enhanced acoustic startle responses as adults, compared to offspring from saline-treated dams. In offspring tested for pre-pulse inhibition (PPI) of acoustic startle and for apomorphine modulation of PPI, no effects of either gestational LPS or of postnatal anoxia and no interactions between LPS and anoxia were observed. It is concluded that maternal LPS exposure during pregnancy in the rat may be a useful model to study mechanisms responsible for effects of maternal infection on behaviors relevant to schizophrenia, in offspring.
精神分裂症发病率的增加与多种围产期损伤有关，最显著的是孕期母体感染和围产期缺氧。本研究使用大鼠模型直接测试孕期母体暴露于细菌内毒素（脂多糖，LPS）是否会改变成年后代中与精神分裂症相关的行为。该研究还测试了产后缺氧是否与孕期LPS暴露相互作用以影响行为。成年后，孕期第18天和第19天给予LPS的母鼠所产后代与生理盐水处理母鼠所产后代相比，苯丙胺诱导的运动明显增加。出生后第7天的缺氧期对苯丙胺诱导的运动没有影响，孕期LPS和产后缺氧对该行为的影响之间也没有相互作用。与生理盐水处理母鼠所产后代相比，LPS处理母鼠的成年后代也表现出增强的听觉惊吓反应。在测试听觉惊吓的前脉冲抑制（PPI）和阿扑吗啡对PPI调节作用的后代中，未观察到孕期LPS或产后缺氧的影响，也未观察到LPS和缺氧之间的相互作用。得出的结论是，大鼠孕期母体暴露于LPS可能是研究母体感染对后代中与精神分裂症相关行为影响的机制的有用模型。
