| Abstract: | Gravid rats exposed to lipopolysaccharide (LPS) produced offspring with fewer dopamine (DA) neurons, have life-long increases in TNF-alpha, and are more susceptible to neurotoxin exposures. We tested the hypothesis that prenatal LPS exposure alters the trophic environment of developing DA neurons. We exposed gravid female rats to Hank’s balanced salt solution (HBSS) or 100,000 endotoxin units of LPS at embryonic day 10.5. The cerebellum (CB), ventral mesencephalon (VM), and lateral ganglionic eminence (striatal; ST) tissues were collected at E14.5 and plated as various co-culture combinations. After seven days, the co-cultures were analyzed for THir cell number, average process length and cell death. Co-cultures established from fetuses prenatally exposed to LPS had fewer TH-ir neurons in the LPS-VM/LPS-ST condition compared with the SAL-VM/SAL-ST and SAL-VM/LPS-ST conditions (F(3, 26) = 19.5, p < 0.001], reduced process lengths (F(1, 31) = 83.53; p < 0.001) and increased cell death (F(3, 31) = 12.46). We analyzed gene expression of brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 (NT-3), Glial-derived neurotrophic factor (GDNF), Fibroblast growth factor- 8 (FGF-8), and ciliary neurotrophic factor (CNTF) by RT-PCR in the CB, VM, and ST brain regions of embryos at E14.5. GDNF and BDNF were both reduced in embryos exposed to LPS while no differences in NT-3, FGF-8 or CNTF were observed. These results suggest that prenatal exposure to LPS alters the trophic environment of the developing nigrostriatal pathway. |
