Moderate prenatal alcohol exposure suppresses the TLR4-mediated innate immune response in the hippocampus of young rats
| Autor: | Li-Xin Shang, Peng Wang, Si-Wei You, Sen Sheng, Fang Kuang, Bo-Ya Liu, Ming-Mei Wu, Xiao-Yan Wei |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_specialty animal structures Lipopolysaccharide Central nervous system Down-Regulation Hippocampus Stimulation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine medicine Animals Receptor Cells Cultured Neuroinflammation Injections Intraventricular Ethanol Tumor Necrosis Factor-alpha business.industry General Neuroscience Interferon-beta Immunity Innate Rats Up-Regulation Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry TRIF Prenatal Exposure Delayed Effects TLR4 Female business 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience Letters. 699:77-83 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2019.01.049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect