Preview

Toxicological Review

Advanced search

THE EXPRESSION AND POLYMORPHISM INFLUENCE OF GENES, ENCODING THE GABA-RECEPTORS, ON SEVERITY OF THE ETHANOL DEPRESSING ACTION IN RATS

Abstract

Expression and polymorphism of encoding the Gaba-receptors of genes, which determine the severity of the depressing effect of ethanol in white outbred rats were studied. In the course of the experiment, genotyping of animals was made using 16 single-nucleotide replacements in genes encoding the GABA. The genetic diversity of allelic variants was revealed, based on 11 polymorphisms. It was found out that in rats with the genotype homozygous variant TT (rs 197587817) the expression level of gene Gabra l (in brain 8 h after administration of ethanol) was authentically lower (2-fold) as compared to the heterozygous genotype CT. An authentic association of the gene Gabrb1 expression level (p<0.05) with the severity degree of the ethanol depressing effect on the nervous system in rats 8 h after administration of the toxicant was demonstrated. 

About the Authors

Natalya Sergeevna Osechkina
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Georgiy Valerevich Nazarov
Scientific Research Test Institute of Military Medicine, S.M. Kirov Medical Military Academy
Russian Federation


Evgeniy Yur’evich Bonitenko
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Maksim Borisovich Ivanov
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Vadim Anatol’evich Kashuro
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Nataliya Vadimovna Lapina
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Aleksandr Vladimirovich Babkin
Scientific Research Test Institute of Military Medicine, S.M. Kirov Medical Military Academy
Russian Federation


Irina Sergeevna Berdinskih
Scientific Research Test Institute of Military Medicine, S.M. Kirov Medical Military Academy
Russian Federation


Aleksandra Sergeevna Melekhova
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Karina Olegovna Voytsekhovich
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Dmitriy Sergeevich Lisitskiy
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Natal’ya Vasil’evna Makarova
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


Tat’yana Vladimirovna Kashina
Federal State Budgetary Science Institution «Institute of Toxicology» of Federal Medico-Biological Agency
Russian Federation


References

1. Bonitenko Yu.Yu. Acute ethanol poisoning and its surrogates. St. Petersburg: ELBI SPB; 2005 (in Russian).

2. Kursov S.V., Mikhnevich K.G., Krivobok V.I. Acute poisoning with ethanol. Medical emergency conditions. 2012; 7-8: 46-7 (in Russian).

3. Stevens R.D., Nyquist P.A. Coma, delirium, and cognitive dysfunction in critical illness. Crit Care Clin. 2006; 22 (4): 787-804.

4. Pigolkin Yu.I. Forensic medical diagnostics alcohol poisoning. M.: Medical News Agency; 2006 (in Russian).

5. Tabakoff B., Khoffman L. Neurobiological effects of alcohol. Addiction issues. 2003; 5: 27-42 (in Russian).

6. Macgregor et al. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis. Human Molecular Genetics. 2009; 18: 580-93.

7. Schumann G., Johann M., Frank J. et al. Systematic analysis of glutaminergic neurotransmission genes in alcohol dependence and adolescent risky drinking behavior. Archives of General Psychiatry. 2008; 65 (7): 826-38.

8. Dolgo-Saburov V.B., Petrov A.N., Lisitskiy D.S., Belyaev V.A. The central neurochemical effects of acute and chronic influence of ethanol. The mechanisms of tolerance and dependence (Review). Biomedical Journal Medline. 2011; 12: 1423-36 (in Russian).

9. Enoch M., Schwartz L., Albaugh B., Virkkunen M., Goldman D. Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism. American Journal of Medical Genetics. 2006; 141: 599-607.

10. Golovko A.I., Barinov V.A., Basharin V.A., Bonitenko E.Ju., Ivanov M.B., Golovko S.I., Lapina N.V. Pharmacological activity of the amethystic agents influencing the gaba and glutamic acid systems. Biomedical Journal Medline. Pharmacology. 2012; 13: 157-84 (in Russian).

11. Pignataro L., Varodayan F.P.,Tannenholz L.E.,Harrison N.L.. The regulation of neuronal gene expression by alcohol. Pharmacology $ Therapeutics Journal. 2009; 124 (3): 324-335.

12. Pignataro L., Miller A.N., Ma L., Alcohol regulates gene expression in neurons via activation of heat shock factor 1. The Journal of Neuroscience. 2007; 27 (47): 12957-66.

13. Basharin V.A. Neuropeptides and substrates of energy metabolism in the treatment of severe poisoning deprimiruyuschie substances: Dis Doctor. Med. Sciences. S-P.; 2011. (in Russian).

14. Protocol: High-Capacity cDNA Reverse Transcription Kits For 200 and 1000 Reactions. Available at: http://tools.lifetechnologies.com/content/sfs/manuals/cms_058198.pdf

15. TaqMan® OpenArray® Genotyping. Getting Started Guide. 2010. Available at: http://tools.lifetechnologies.com/content/ sfs/manuals/cms_058198.pdf.

16. Relative Quantitation Using Comparative Ct Getting Started Guide for the 7900HT Fast System.

17. Misiurin V.A. Investigation of the features of expression and prevalence of testicular cancer-gene: Dis Candidate Biol of Sciences. M.; 2014 (in Russian).

18. Duan J., Antezana M.A. Mammalian mutation pressure, synonymous codon choice, and mRNA degradation. J Mol Evol. 2003; 57 (6): 694-01.


Review

For citations:


Osechkina N.S., Nazarov G.V., Bonitenko E.Yu., Ivanov M.B., Kashuro V.A., Lapina N.V., Babkin A.V., Berdinskih I.S., Melekhova A.S., Voytsekhovich K.O., Lisitskiy D.S., Makarova N.V., Kashina T.V. THE EXPRESSION AND POLYMORPHISM INFLUENCE OF GENES, ENCODING THE GABA-RECEPTORS, ON SEVERITY OF THE ETHANOL DEPRESSING ACTION IN RATS. Toxicological Review. 2014;(6):22-27. (In Russ.)

Views: 213


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0869-7922 (Print)