Prenatal alcohol exposure (PAE) can lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in the development of defects in the nervous system caused by PAE. However, how PAE affects the TLR4 response in the brain remains unclear. Using the model of semi-forced alcoholization of pregnant rats, we investigated TLR4-mediated signaling on the 30th day of postnatal development in their offspring. Rats exposed to PAE showed a higher expression of proinflammatory cytokines in the prefrontal cortex, but TLR4-mediated signaling in response to lipopolysaccharide (LPS) was weakened. These data suggest that PAE can lead to neuroinflammation and suppression of the TLR4-mediated response to LPS in the prefrontal cortex of young rats. Since innate immunity plays an important role in brain development, PAE-induced suppression of the TLR4-mediated response may be one of the mechanisms for the development of CNS pathology.
Prenatal'noe vozdeĭstvie alkogolia (PVA) mozhet privesti k narusheniiam razvitiia tsentral'noĭ nervnoĭ sistemy (TsNS) i umstvennoĭ otstalosti. Toll-podobnyĭ retseptor (TLR) 4 igraet vazhnuiu rol' v razvitii defektov nervnoĭ sistemy, vyzvannykh PVA. Odnako to, kak PVA vliiaet na otvet TLR4 v golovnom mozge, ostaetsia neiasnym. Ispol'zuia model' poluprinuditel'noĭ alkogolizatsii beremennykh krys, my issledovali TLR4-oposredovannuiu signalizatsiiu na 30-ĭ den' postnatal'nogo razvitiia u ikh potomstva. U krys, podvergnutykh PVA, otmechena bolee vysokaia ékspressiia provospalitel'nykh tsitokinov v prefrontal'noĭ kore, no oslablena TLR4-oposredovannaia signalizatsiia v otvet na lipopolisakharid (LPS). Éti dannye pozvoliaiut predpolozhit', chto PVA mozhet privodit' k neĭrovospaleniiu i podavleniiu TLR4-oposredovannogo otveta na LPS v prefrontal'noĭ kore golovnogo mozga molodykh krys. Poskol'ku vrozhdennyĭ immunitet igraet vazhnuiu rol' v razvitii mozga, PVA-indutsirovannoe podavlenie TLR4-oposredovannogo otveta mozhet byt' odnim iz mekhanizmov razvitiia patologii TsNS.
Keywords: alcohol; brain; neuroinflammation; pregnancy; rats.