Correction of hematopoiesis in alcoholism by the lymphocytes, modulated with a synthetic GABAA-R ligand

Introduction It is well known that alcohol has a variety of pathologic effects on hematopoiesis. Long term alcohol abuse result in a significant suppression of both the production of blood cells and structural changes in precursors, namely the suppression of their maturation, up to pancytopenia. We first demonstrated the immunomodulatory properties of a synthetic GABAA-R ligand, meta-chlorobenzhydrylurea (m-CBU). We also showed that splenic lymphocytes modulated in vitro by m-CBU after intravenous administration to syngeneic long-term alcoholized recipients have a positive effect, manifested in the editing of behavior characteristic of alcoholism against the background of stimulation neuroplasticity and reduction of neuroinflammation. Objectives The purpose of this work was to study bone marrow hematopoiesis and peripheral blood parameters in long-term alcoholized recipients after transplantation of syngeneic lymphocytes modulated in vitro by m-CBU. Methods Male (CBAxC57Bl/6)F1 mice with 6-month 10% ethanol exposure were undergoing the transplantation of syngeneic long-term alcoholized mice lymphocytes, pretreated in vitro with m-CBU. The number of bone marrow hematopoietic progenitors and cellular composition of the blood were assessed in the recipients. Results Long-term alcoholization in mice led to a decrease in the colony-forming activity of hematopoietic precursors, mainly erythroid; in the peripheral blood of mice, a significant decrease in the number of erythrocytes, leukocytes, lymphocytes and platelets was recorded, while the population of segmented neutrophils significantly increased. Lymphocytes, precultured with m-CBU, in syngeneic long-term alcoholized recipients had a corrective effect on a number of hematopoietic parameters (colony-forming activity of erythroid precursors in the bone marrow, the number of erythrocytes, segmented neutrophils and lymphocytes in the peripheral blood) to indicators comparable to those in intact mice of the corresponding with tendency to increase the number of platelets in the peripheral blood. Conclusions The data obtained may indicate the effectiveness of m-CBU -modulated lymphocytes transplantation in correcting a number of changes in hematopoiesis provoked by long-term alcohol abuse. Disclosure of Interest None Declared

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Journal
European Psychiatry
Published
2025-04-01
DOI
https://doi.org/10.1192/j.eurpsy.2025.2031
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
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article
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article

Correction of hematopoiesis in alcoholism by the lymphocytes, modulated with a synthetic GABAA-R ligand

E. Markova, M. Knyazheva, O. Anikeeva, I. Savkin et al.
European Psychiatry
Neuroinflammation and Neurodegeneration Mechanisms
article

Correction of hematopoiesis in alcoholism by the lymphocytes, modulated with a synthetic GABAA-R ligand

E. Markova, M. Knyazheva, O. Anikeeva, I. Savkin, I. А. Orlovskaya
article en

Abstract

Introduction It is well known that alcohol has a variety of pathologic effects on hematopoiesis. Long term alcohol abuse result in a significant suppression of both the production of blood cells and structural changes in precursors, namely the suppression of their maturation, up to pancytopenia. We first demonstrated the immunomodulatory properties of a synthetic GABAA-R ligand, meta-chlorobenzhydrylurea (m-CBU). We also showed that splenic lymphocytes modulated in vitro by m-CBU after intravenous administration to syngeneic long-term alcoholized recipients have a positive effect, manifested in the editing of behavior characteristic of alcoholism against the background of stimulation neuroplasticity and reduction of neuroinflammation. Objectives The purpose of this work was to study bone marrow hematopoiesis and peripheral blood parameters in long-term alcoholized recipients after transplantation of syngeneic lymphocytes modulated in vitro by m-CBU. Methods Male (CBAxC57Bl/6)F1 mice with 6-month 10% ethanol exposure were undergoing the transplantation of syngeneic long-term alcoholized mice lymphocytes, pretreated in vitro with m-CBU. The number of bone marrow hematopoietic progenitors and cellular composition of the blood were assessed in the recipients. Results Long-term alcoholization in mice led to a decrease in the colony-forming activity of hematopoietic precursors, mainly erythroid; in the peripheral blood of mice, a significant decrease in the number of erythrocytes, leukocytes, lymphocytes and platelets was recorded, while the population of segmented neutrophils significantly increased. Lymphocytes, precultured with m-CBU, in syngeneic long-term alcoholized recipients had a corrective effect on a number of hematopoietic parameters (colony-forming activity of erythroid precursors in the bone marrow, the number of erythrocytes, segmented neutrophils and lymphocytes in the peripheral blood) to indicators comparable to those in intact mice of the corresponding with tendency to increase the number of platelets in the peripheral blood. Conclusions The data obtained may indicate the effectiveness of m-CBU -modulated lymphocytes transplantation in correcting a number of changes in hematopoiesis provoked by long-term alcohol abuse. Disclosure of Interest None Declared

European PsychiatryVol. 68(S1)
Research Institute of Fundamental and Clinical Immunology (RU), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK)
Openalex Percentile: Top 69%
Neuroinflammation and Neurodegeneration Mechanisms
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