1. Institute of Experimental Medicine, St. Petersburg, Russia; Military Medical Academy of S.M. Kirov, St. Petersburg, Russia 2. Institute of Experimental Medicine, St. Petersburg, Russia; North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia 3. Institute of Experimental Medicine, St. Petersburg, Russia
Ethanol causes long-term changes in the toll-like receptor (TLR) system, promoting activation of neuroinflammation pathways. Alcohol use during pregnancy causes neuroinflammatory processes in the fetus; this can lead to the development of symptoms of fetal alcohol spectrum disorder (FASD). Our study has shown that prenatal alcohol exposure (PAE) induced long-term changes in the TLR system genes (Tlr3, Tlr4, Ticam, Hmgb1, cytokine genes) in the forebrain cortex of rat pups. Administration of rifampicin (Rif), which can reduce the level of pro-inflammatory mediators in various pathological conditions of the nervous system, normalized the altered expression level of the studied TLR system genes. This suggests that Rif can prevent the development of persistent neuroinflammatory events in the forebrain cortex of rat pups caused by dysregulation in the TLR system.
Airapetov M.I., Eresko S.O., Ignatova P.D., Skabelkin D.A., Mikhailova A.A., Ganshina D.A., Lebedev A.A., Bychkov E.R., Shabanov P.D. (2023) The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol. Biomeditsinskaya Khimiya, 69(4), 228-234.
Airapetov M.I. et al. The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol // Biomeditsinskaya Khimiya. - 2023. - V. 69. -N 4. - P. 228-234.
Airapetov M.I. et al., "The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol." Biomeditsinskaya Khimiya 69.4 (2023): 228-234.
Airapetov, M. I., Eresko, S. O., Ignatova, P. D., Skabelkin, D. A., Mikhailova, A. A., Ganshina, D. A., Lebedev, A. A., Bychkov, E. R., Shabanov, P. D. (2023). The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol. Biomeditsinskaya Khimiya, 69(4), 228-234.
References
Couch A.C.M., Berger T., Hanger B., Matuleviciute R., Srivastava D.P., Thuret S., Vernon A.C. (2021) Maternal immune activation primes deficiencies in adult hippocampal neurogenesis. Brain. Behav. Immun., 97, 410-422. CrossRef Scholar google search
Nolvi S., Merz E.C., Kataja E.L., Parsons C.E. (2022) Prenatal stress and the developing brain: Postnatal environments promoting resilience. Biol. Psychiatry, 93(10), 942-952. CrossRef Scholar google search
Woods R.M., Lorusso J.M., Potter H.G., Neill J.C., Glazier J.D., Hager R. (2021) Maternal immune activation in rodent models: A systematic review of neurodevelopmental changes in gene expression and epigenetic modulation in the offspring brain. Neurosci. Biobehav. Rev., 129, 389-421. CrossRef Scholar google search
Usui N., Kobayashi H., Shimada S. (2023) Neuroinflammation and oxidative stress in the pathogenesis of autism spectrum disorder. Int. J. Mol. Sci., 24(6), 5487. CrossRef Scholar google search
Mattson S.N., Bernes G.A., Doyle L.R. (2019) Fetal alcohol spectrum disorders: A review of the neurobehavioral deficits associated with prenatal alcohol exposure. Alcohol. Clin. Exp. Res., 43(6), 1046-1062. CrossRef Scholar google search
Shabanov P.D., Kalishevich S.Yu. (1998) Biology of Alcoholism. Lan', 272 p. Scholar google search
Ajrapetyancz M.G. (1989) Posledstviya Alkogol`noj Intoksikaczii Dlya Potomstva, Nauka, Moskva, 124 p. Scholar google search
Siegel A., Zalcman S.S. (2008) The Neuroimmunological Basis of Behavior and Mental Disorders, Springer, USA, 454 p. CrossRef Scholar google search
Wang X., Grace P.M., Pham M.N., Cheng K., Strand K.A., Smith C., Li J., Watkins L.R., Yin H. (2013) Rifampin inhibits toll-like receptor 4 signaling by targeting myeloid differentiation protein 2 and attenuates neuropathic pain. FASEB J., 27(7), 2713-2722. CrossRef Scholar google search
Bi W., Zhu L., Jing X., Zeng Z., Liang Y., Xu A., Liu J., Xiao S., Yang L., Shi Q., Guo L., Tao E. (2014) Rifampicin improves neuronal apoptosis in LPS-stimulated co-cultured BV2 cells through inhibition of the TLR-4 pathway. Mol. Med. Rep., 10(4), 1793-1799. CrossRef Scholar google search
Bi W., Cheng X., Zeng Z., Zhou R., Luo R., Zhang J., Zhu L. (2021) Rifampicin ameliorates lipopolysaccharide-induced cognitive and motor impairments via inhibition of the TLR4/MyD88/NF-κB signaling pathway in mice. Neurol. Res., 43(5), 358-371. CrossRef Scholar google search
Zahednasab H., Firouzi M., Kaboudanian-Ardestani S., Mojallal-Tabatabaei Z., Karampour S., Keyvani H. (2019) The protective effect of rifampicin on behavioral deficits, biochemical, and neuropathological changes in a cuprizone model of demyelination. Cytokine, 113, 417-426. CrossRef Scholar google search
Livak K.J., Schmittgen T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods., 25(4), 402-408. CrossRef Scholar google search
Airapetov M., Eresko S., Lebedev A., Bychkov E., Shabanov P. (2021) The role of toll-like receptors in neurobiology of alcoholism. BioScience Trends, 15(2), 74-82. CrossRef Scholar google search
Airapetov M.I., Eresko S.O., Bychkov E.R., Lebedev A.A., Shabanov P.D. (2020) The expression level of toll-like receptors changes in the emotiogenic brain structures of rats under conditions of prolonged alcoholization and ethanol withdrawal. Medical Immunology, 22(1), 77-86. CrossRef Scholar google search
Airapetov M.I., Eresko S.O., Kochkin D.V., Bychkov E.R., Lebedev A.A., Shabanov P.D. (2022) Ginsenosides affect the system of toll-like receptors in the brain of rats under conditions of long-term alcohol withdrawal. Biomeditsinskaya Khimiya, 68(6), 459-469. CrossRef Scholar google search
Coleman L.G., Zou J., Crews F.T. (2017) Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7. J. Neuroinflammation, 14(1), 1-15. CrossRef Scholar google search
Gano A., Lebonville C.L., Becker H.C. (2022) TLR3 activation with poly I:C exacerbates escalated alcohol consumption in dependent male C57BL/6J mice. Am. J. Drug Alcohol Abuse, 12, 1-12. CrossRef Scholar google search
Lawrimore C.J., Coleman L.G., Crews F.T. (2019) Ethanol induces interferon expression in neurons via TRAIL: Role of astrocyte-to-neuron signaling. Psychopharmacology (Berlin), 236(10), 2881-2897. CrossRef Scholar google search
Qin L., Zou J., Barnett A., Vetreno R.P., Crews F.T., Coleman L.G. Jr. (2021) TRAIL mediates neuronal death in AUD: A link between neuroinflammation and neurodegeneration. Int. J. Mol. Sci., 22(5), 2547. CrossRef Scholar google search
Rizzo M.D., Crawford R.B., Bach A., Sermet S., Amalfitano A., Kaminski N.E. (2019) Imiquimod and interferon-alpha augment monocyte-mediated astrocyte secretion of MCP-1, IL-6, and IP-10 in a human co-culture system. J. Neuroimmunol., 333, 576969. CrossRef Scholar google search
Chen T., Chen C., Zhang Z., Zou Y., Peng M., Wang Y. (2016) Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice. Brain Behav. Immun., 56, 42-55. CrossRef Scholar google search
Alfonso-Loeches S., Pascual-Lucas M., Blanco A.M., Sanchez-Vera I., Guerri C. (2010) Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. J. Neurosci., 30(24), 8285-8295. CrossRef Scholar google search
Ferguson C., McKay M., Harris R.A., Homanics G.E. (2013) Toll-like receptor 4 (Tlr4) knockout rats produced by transcriptional activator-like effector nuclease (TALEN)- mediated gene inactivation. Alcohol, 47(8), 595-599. CrossRef Scholar google search
Shukla P.K., Meena A.S., Rao R., Rao R. (2018) Deletion of TLR-4 attenuates fetal alcohol exposure-induced gene expression and social interaction deficits. Alcohol, 73, 73-78. CrossRef Scholar google search
Wang P., Liu B.-Y., Wu M.-M., Wei X.-Y., Sheng S., You S.-W., Shang L.-X., Kuang F. (2019) Moderate prenatal alcohol exposure suppresses the TLR4-mediated innate immune response in the hippocampus of young rats. Neurosci. Lett., 699, 77-83. CrossRef Scholar google search
Airapetov M.I., Eresko S.O., Skabelkin D.A., Iskalieva A.R., Lebedev A.A., Bychkov E.R., Shabanov P.D. (2022) The effect of rifampicin on the system of toll-like receptors in the nucleus accumbens of the brain of long-term alcoholized rats during alcohol withdrawal. Biomeditsinskaya Khimiya, 68(4), 279-287. CrossRef Scholar google search
Kaul D., Habbel P., Derkow K., Krüger C., Franzoni E., Wulczyn F.G., Bereswill S., Nitsch R., Schott E., Veh R., Naumann T., Lehnardt S. (2012) Expression of toll-like receptors in the developing brain. PLoS One., 7(5), e37767. CrossRef Scholar google search
MacDowell K.S., Munarriz-Cuezva E., Caso J.R., Madrigal J.L.M., Zabala A., Meana J.J., García-Bueno B., Leza J.C. (2017) Paliperidone reverts toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia. Neuropharmacology, 116, 196-207. CrossRef Scholar google search
O'Loughlin E., Pakan J.M.P., Yilmazer-Hanke D., McDermott K.W. (2017) Acute in utero exposure to lipopolysaccharide induces inflammation in the pre- and postnatal brain and alters the glial cytoarchitecture in the developing amygdala. J. Neuroinflammation, 14(1), 212. CrossRef Scholar google search
Ali A.E., Mahdy H.M., Elsherbiny D.M., Azab S.S. (2018) Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries. Biochem. Pharmacol., 156, 431-443. CrossRef Scholar google search
Qosa H., Abuznait A.H., Hill R.A., Kaddoumi A. (2012) Enhanced brain amyloid-β clearance by rifampicin and caffeine as a possible protective mechanism against Alzheimer's disease. J. Alzheimers Dis., 31(1), 151-165. CrossRef Scholar google search
Acuña L., Hamadat S., Corbalán N.S. (2019) Rifampicin and its derivative rifampicin quinone reduce microglial inflammatory responses and neurodegeneration induced in vitro by α-synuclein fibrillary aggregates. Cells, 8(8), 776. CrossRef Scholar google search
Acuña L., Corbalán N.S., Raisman-Vozari R. (2020) Rifampicin quinone pretreatment improves neuronal survival by modulating microglia inflammation induced by α-synuclein. Neural. Regen. Res., 15(8), 1473-1474. CrossRef Scholar google search
Airapetov M.I., Eresko S.O., Bychkov E.R., Lebedev A.A., Shabanov P.D. (2021) Hmgb1 gene expression changes in the striatum and amigdal of the rat's brain under alcoholization and ethanol withdrawal. Biomeditsinskaya Khimiya, 67(1), 95-99. CrossRef Scholar google search
Blednov Y.A., Ponomarev I., Geil C., Bergeson S., Koob G.F., Harris R.A. (2012) Neuroimmune regulation of alcohol consumption: Behavioral validation of genes obtained from genomic studies. Addiction Biology, 17(1), 108-120. CrossRef Scholar google search
