The study of dextromethorphan treatment on preventing prenatal LPS exposure induced reduction in dopamine & serotonin neuron and neurogenesis
| Autor: | Chia-Yu Huang, 黃嘉宇 |
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| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Recently many studies have shown that maternal infection during pregnancy will affect neural development of fetal brain, and increase the risks of offspring suffering from mental disorders. Infection during pregnancy is very common, which could increase maternal cytokine in serum and expose the embryo to high cytokine environment therefore affecting their neural development. In the present studies, we used lipopolysaccharide (LPS) injection in the early stage of pregnancy to simulate mild bacterial infection, and investigate offspring dopamine (DA) and serotonin (5-HT) neurons, neurogenesis, as well as the responses to secondary LPS exposure. We also investigated whether dextromethorphan (DM), an anti-inflammatory drug, could inhibit the inflammation and reduce the neural damage. Experiments used pregnant Sprague-Dawley (SD) rats. Pregnant rats were given LPS (66μg/kg) or phosphate buffered saline (PBS) injections on E10.5 day. The P7 offspring were sacrificed 2, 4, 6 and 12 hours after secondary LPS or PBS injection to measure serum cytokine levels and DA, 5-HT cell numbers in the brain. In another group of pregnant rats we injected LPS, and 1h and 24h later injected DM (30mg/kg) or vehicle (ddH2O). Part of the offspring from this group were sacrificed 2 hours after secondary LPS or PBS injection on P7 to measure serum cytokine levels, and part of the offspring were sacrificed on P30 to measure DA and 5-HT cell numbers in the brain. We also used P60 offspring from this group to study adult neurogenesis by bromodeoxyuridine (BrdU, 200 mg/kg) injection. We found that prenatal LPS exposure increased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations; and decreased DA cells in substantia nigra and 5-HT cells in dorsal raphe of P7 rat which were given secondary LPS injections. The P30 rats of LPS+DM group showed that DM could reverse the DA cells reduction caused by prenatal LPS exposure, but not the reduction of 5-HT cells. The P60 rats of LPS+Vehicle group showed reduction in neurogenesis in subventricular zone (SVZ) and proliferation in hippocampal dentate gyrus. However, DM treatment could not reverse the reduction in neurogenesis and proliferation. We conclude that anti-inflammatory activity of DM could reduce LPS-induced maternal immune response and show protective effects for DA neurons in offspring. Furthermore, our results provide evidences that DM might moderate the impact of combined prenatal and postnatal LPS injections, based on the reduction in basal levels of cytokines and the reduction in enhanced cytokine production following secondary LPS injection in offspring. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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