Moderate prenatal alcohol exposure suppresses the TLR4-mediated innate immune response in the hippocampus of young rats.
Prenatal alcohol exposure (PAE) could lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in PAE-induced neurodevelopmental defects. However, how PAE affects TLR4 response in the brain remains controversial. Using a moderate PAE model by feeding pregnant rats with liquid ethanol diet, we investigated the TLR4-mediated response to intraventricular injection of lipopolysaccharide (LPS) in the hippocampus of PEA rats at postnatal day (PND) 30. The results showed that PAE significantly up-regulated the expression of Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor protein inducing interferon (IFN)-β (TRIF), TNF-α, and IL-1β in the rat hippocampus in the absence of LPS, indicated by western blot assay. LPS treatment dramatically up-regulated the expressions of TLR4 and its downstream molecules in the hippocampus of paired-food and control groups. But no such significant changes of those molecules were found in the hippocampus of PAE animals. Moreover, the LPS stimulation even down-regulated the levels of TLR4 and TRIF in the PAE group. These data suggest that the relatively moderate level of PAE may lead to a mild neuroinflammation and a suppression of TLR4-mediated response to LPS in the hippocampus of young rats. As innate immunity plays crucial roles in CNS development, moderate PAE-induced suppression of TLR4-mediated response may serve as a new candidate mechanism of CNS developmental defects.
['Wang|Peng|P|', 'Liu|Bo-Ya|BY|', 'Wu|Ming-Mei|MM|', 'Wei|Xiao-Yan|XY|', 'Sheng|Sen|S|', 'You|Si-Wei|SW|', 'Shang|Li-Xin|LX|', 'Kuang|Fang|F|']
D033942:Adaptor Proteins, Vesicular Transport D000818:Animals D002478:Cells, Cultured D015536:Down-Regulation D000431:Ethanol D005260:Female D006624:Hippocampus D007113:Immunity, Innate D007276:Injections, Intraventricular D016899:Interferon-beta D008070:Lipopolysaccharides D008297:Male D011247:Pregnancy D011297:Prenatal Exposure Delayed Effects D051381:Rats D051197:Toll-Like Receptor 4 D014409:Tumor Necrosis Factor-alpha D015854:Up-Regulation
Prenatal alcohol exposure Innate immune Hippocampus Rat TLR4 LPS