| Summary: | 碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 103 === Maternal infection during pregnancy has been shown to affect fetal brain development and lead to increased risk of psychiatric disorders in offspring. In recent years, many studies have shown the association between cytokine and depression. In the present studies, we used lipopolysaccharide (LPS) injection in the early stage of pregnancy to simulate mild bacterial infection and investigate cytokine changes in maternal serum and fetal amniotic fluid. We also investigated whether fetal dopamine (DA) and serotonin (5-HT) neuron express cytokine receptors and examined the changes in the number of DA and 5-HT neurons. In addition, the effects of maternal behavior on cytokine levels in LPS exposed offspring were studied. Experiments used pregnant Sprague-Dawley (SD) rats. Pregnant rats were given LPS (66μg/kg) or phosphate buffered saline (PBS, 1 ml/kg) injections on E12.5 day. The rats were sacrificed 2, 6, 12 and 24 hours after injection to measure cytokine levels in maternal serum and amniotic fluid. In another group of pregnant rats we injected bromodeoxyuridine (BrdU; 200 mg/kg/day) from E9.5 to E11.5 and inject LPS on E12.5. The offspring were sacrificed on P1, P7, P14, P21 and P30 to measure serum cytokine levels and DA, 5-HT cell numbers in the brain. LPS treatment increased interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations in maternal serum and fetal amniotic fluid. Offspring exposed to LPS showed increase in IL-6 and IL-10 concentration in serum. Serotonin-1A (5HT1A) receptor protein was decreased in embryonic neural tube and DA and 5-HT cell numbers were decreased. In addition, we found DA neuron expressed IL-6 receptor subunit gp130 and 5-HT neuron expressed IL-6 receptor (IL-6R) and TNF receptor-1 (TNFR1). Cell numbers of DA neuron in substantia nigra and 5-HT neuron in raphe nucleus were decreased and the BrdU experiment showed reduced cell proliferation of DA and 5-HT cell. We concluded that LPS-induced maternal immune response leads to significant increase in cytokines IL-6, TNF-α, and IL-10. Therefore, the cytokine might regulate DA and 5-HT neuron development through cytokine receptors on DA and 5-HT cell surface. Furthermore, we found that the reduction in DA and 5-HT cell number might be due to reduced cell proliferation.
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