E. V. Markova, I. V. Savkin, E. V. Serenko, M. A. Knyazheva, Yu. A. Shevchenko
{"title":"The Central Effects of Peripherally Administered Immune Cells Modulated by an Original Anticonvulsant in Experimental Alcoholism","authors":"E. V. Markova, I. V. Savkin, E. V. Serenko, M. A. Knyazheva, Yu. A. Shevchenko","doi":"10.1134/s1819712423030121","DOIUrl":null,"url":null,"abstract":"<p><b>Abstract</b>—Disruption of neuroimmune regulatory relationships caused by a change in the functional phenotype of immune cells due to chronic ethanol intoxication is an essential link in the pathogenesis of alcoholism. The unidirectional influence of most psychoactive drugs on the cells of the nervous and immune systems allows one to consider immune cells as model objects for influencing intersystem functional relationships. Based upon our own priority data on the presence of immunomodulatory properties of the original anticonvulsant acting on the molecular targets of ethanol in the central nervous system and the immune system in chronic alcohol intoxication, the aim of the present study was to evaluate the central effects of peripherally injected lymphocytes with the in vitro modulated functional activity by a synthetic ligand of the GABAA-receptor complex <i>meta</i>-chlorobenzhydrylurea in long-term alcoholized animals. It was shown that transplantation of lymphocytes precultured with the anticonvulsant in syngeneic long-term alcoholic recipients achieves a decrease in alcohol motivation and stimulation of behavioral activity in the “open field” test. Editing of behavioral patterns characteristic of chronic alcohol intoxication was recorded against the background of a decrease in proinflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ and an increase in the anti-inflammatory cytokine IL-10 in pathogenetically significant brain structures, as well as an increase in the level of BDNF in the hippocampus, which allows us to consider a decrease in neuroinflammation and stimulation neuroplasticity as possible mechanisms for modification of the behavior of recipients. Visualization of functionally active lymphocytes precultured with <i>meta</i>-chlorobenzhydrylurea in the brain parenchyma of long-term alcoholized recipients also suggests a direct effect of injected lymphocytes on CNS cells. Thus, immune cells modulated in vitro with <i>meta</i>-chlorobenzhydrylurea by relatively independent mechanisms have positive psychoneuromodulating effects in chronic ethanol intoxication, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1134/s1819712423030121","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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Abstract—Disruption of neuroimmune regulatory relationships caused by a change in the functional phenotype of immune cells due to chronic ethanol intoxication is an essential link in the pathogenesis of alcoholism. The unidirectional influence of most psychoactive drugs on the cells of the nervous and immune systems allows one to consider immune cells as model objects for influencing intersystem functional relationships. Based upon our own priority data on the presence of immunomodulatory properties of the original anticonvulsant acting on the molecular targets of ethanol in the central nervous system and the immune system in chronic alcohol intoxication, the aim of the present study was to evaluate the central effects of peripherally injected lymphocytes with the in vitro modulated functional activity by a synthetic ligand of the GABAA-receptor complex meta-chlorobenzhydrylurea in long-term alcoholized animals. It was shown that transplantation of lymphocytes precultured with the anticonvulsant in syngeneic long-term alcoholic recipients achieves a decrease in alcohol motivation and stimulation of behavioral activity in the “open field” test. Editing of behavioral patterns characteristic of chronic alcohol intoxication was recorded against the background of a decrease in proinflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ and an increase in the anti-inflammatory cytokine IL-10 in pathogenetically significant brain structures, as well as an increase in the level of BDNF in the hippocampus, which allows us to consider a decrease in neuroinflammation and stimulation neuroplasticity as possible mechanisms for modification of the behavior of recipients. Visualization of functionally active lymphocytes precultured with meta-chlorobenzhydrylurea in the brain parenchyma of long-term alcoholized recipients also suggests a direct effect of injected lymphocytes on CNS cells. Thus, immune cells modulated in vitro with meta-chlorobenzhydrylurea by relatively independent mechanisms have positive psychoneuromodulating effects in chronic ethanol intoxication, which makes it possible to consider adoptive immunotherapy as a promising method in the treatment of alcoholism.
期刊介绍：
Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components.
The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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