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Prenatal Exposure to Alcohol Alters TLR4 Mediated Signaling in the Prefrontal Cortex in Rats

Abstract

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 have 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.

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ACKNOWLEDGMENTS

The authors are grateful to the associate professor of the St. Petersburg State Pediatric Medical University L.D. Balashov for the providing experimental animals and assistance in conducting the experiment.

Funding

The study was supported by the Institute of Experimental Medicine within the framework of the State Assignment “Pharmacological analysis of the action of neurotropic drugs, the study of intracellular targets and the creation of targeted delivery systems”, code 0557-2019-0004, and also by the Saint-Petersburg State Pediatric Medical University. The study was supported by a grant from St. Petersburg in the field of scientific, scientific and technical activities in the form of subsidies, the project “Study and correction of the mechanisms of activation of the innate immune system in the brain under conditions of prolonged consumption of ethanol” was approved by the order of the Committee on Science and Higher Education dated December 22, 2020 no. 277 “On the recipients of grants in St. Petersburg in the field of scientific and scientific and technical activities, the amount of grants provided to them in 2020.”

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Correspondence to M. I. Airapetov.

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The authors declare that they have no conflicts of interest. All methods used in this study corresponded to international standards and were approved by the Ethics Committee for the Care and Use of Animals of the Institute of Experimental Medicine (protocol no. 21/5 of February 26, 2015).

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Translated by A. Medvedev

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Airapetov, M.I., Eresko, S.O., Bychkov, E.R. et al. Prenatal Exposure to Alcohol Alters TLR4 Mediated Signaling in the Prefrontal Cortex in Rats. Biochem. Moscow Suppl. Ser. B 16, 134–139 (2022). https://doi.org/10.1134/S1990750822020032

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  • DOI: https://doi.org/10.1134/S1990750822020032

Keywords:

  • rats
  • pregnancy
  • alcohol
  • brain
  • neuroinflammation