1. Institute of Experimental Medicine, St. Petersburg, Russia; St. Petersburg State Medical Pediatric University, St. Petersburg, Russia 2. University ITMO (National Research University), St. Petersburg, Russia 3. Institute of Experimental Medicine, St. Petersburg, Russia 4. Institute of Experimental Medicine, St. Petersburg, Russia; Kirov Military Medical Academy, St. Petersburg, Russia
Alcohol use is a global socially significant problem that remains one of the leading risk factors for disability and premature death. One of the main pathological characteristics of alcoholism is the loss of cognitive control over the amount of consumed alcohol. Growing body of evidence suggests that alterations of neuroimmune communication occurring in the brain during prolonged alcoholization are one of the main mechanisms responsible for the development of this pathology. Ethanol consumption leads to activation of neuroimmune signaling in the central nervous system through many types of Toll-like receptors (TLRs), as well as the release of their endogenous agonists (HMGB1 protein, S100 protein, heat shock proteins, extracellular matrix breakdown proteins). Activation of TLRs triggers intracellular molecular cascades leading to increased expression of the innate immune system genes, particularly proinflammatory cytokines, subsequently causing the development of a persistent neuroinflammatory process in the central nervous system, which results in massive death of neurons and glial cells in the brain structures, which are primarily associated with the development of a pathological craving for alcohol. In addition, some subtypes of TLRs are capable of forming heterodimers with neuropeptide receptors (corticoliberin, orexin, ghrelin receptors), and may also have other functional relationships.
Airapetov M.I. et al. Involvement of TOLL-like receptors in the neuroimmunology of alcoholism // Biomeditsinskaya khimiya. - 2020. - V. 66. -N 3. - P. 208-215.
Airapetov M.I. et al., "Involvement of TOLL-like receptors in the neuroimmunology of alcoholism." Biomeditsinskaya khimiya 66.3 (2020): 208-215.
Airapetov, M. I., Eresko, S. O., Lebedev, A. A., Bychkov, E. R., Shabanov, P. D. (2020). Involvement of TOLL-like receptors in the neuroimmunology of alcoholism. Biomeditsinskaya khimiya, 66(3), 208-215.
Lewohl J.M., Wang L., Miles M.F., Zhang L., Dodd P.R., Harris R.A. (2000) Alcoholism: Clinical and Experimental Research, 24(12), 1873-1882. CrossRef Scholar google search