Maternal infection during pregnancy may affect fetal brain development and lead to neurological and mental disorders. Previously, we used lipopolysaccharide [LPS, 33μg/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.
Bibliographical noteFunding Information:
This study was supported by a research grant to S.W. from the National Science Council of Taiwan (Grant number NSC97-2314-B-400-002-MY3). We thank Dr. Chung-Shi Yang and Mr. Te-Haw Wu for their assistance with the HPLC experiments.
- Maternal infection