Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Brain Behav Immun. 2012 Mar;26(3):459-68. doi: 10.1016/j.bbi.2011.12.003. Epub 2011 Dec 17.
Maternal infection during pregnancy may affect fetal brain development and lead to neurological and mental disorders. Previously, we used lipopolysaccharide [LPS, 33 μg/kg, intraperitoneal injection] exposure on gestation day 10.5 to mimic maternal bacterial infection in rats and found reduced dopaminergic and serotoninergic neurons in the offspring. In the present study, we examined the anxiety and stress responses of the affected offspring and the neurophysiological changes in their brains. Our results show that LPS rats displayed more anxiety-like behaviors and heightened stress responses. Dopamine (DA) in the nucleus accumbens and serotonin (5-HT) in the medial prefrontal cortex and the hippocampus were significantly reduced in LPS rats. Their glucocorticoid receptors in the dorsal hippocampus and the 5-HT(1A) receptors in the dorsal and ventral hippocampus were also reduced. In addition, chronic but not acute fluoxetine treatment reversed the behavioral changes and increased hippocampal 5-HT(1A) receptor expression. This study demonstrates that LPS exposure during a critical time of embryonic development could produce long-term reduction of DA and 5-HT and other neurophysiological changes; such alterations may be associated with the increases in stress response and anxiety-like behaviors in the offspring.
母体在妊娠期间的感染可能会影响胎儿的大脑发育，并导致神经和精神障碍。此前，我们曾在妊娠第 10.5 天通过腹腔注射脂多糖（LPS，33μg/kg）来模拟母体细菌感染，发现子代的多巴胺能和 5-羟色胺能神经元减少。在本研究中，我们检测了受影响后代的焦虑和应激反应以及其大脑的神经生理变化。结果表明，LPS 组大鼠表现出更多的类焦虑行为和更高的应激反应。LPS 组大鼠的伏隔核多巴胺（DA）和内侧前额叶皮质及海马 5-羟色胺（5-HT）明显减少，背侧海马的糖皮质激素受体和背侧及腹侧海马的 5-HT1A 受体也减少。此外，慢性而非急性氟西汀治疗可逆转行为改变并增加海马 5-HT1A 受体表达。本研究表明，胚胎发育关键时期的 LPS 暴露可导致 DA 和 5-HT 等神经生理变化长期减少；这种改变可能与子代应激反应和类焦虑行为的增加有关。
