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The effects of chronic alcoholization on the expression of brain-derived neurotrophic factor and its receptors in the brains of mice genetically predisposed to depressive-like behavior

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Abstract

Brain-derived neurotropic factor (BDNF) plays an important role in mechanisms of depression. Precursor protein of this factor (proBDNF) can initiate apoptosis in the brain, while the mature form of BDNF is involved in neurogenesis. It is known that chronic alcoholization leads to the activation of apoptotic processes, neurodegeneration, brain injury, and cognitive dysfunction. In this work, we have studied the influence of long-term ethanol exposure on the proBDNF and BDNF protein levels, as well as on the expression of genes that encode these proteins in the brain structures of ASC mice with genetic predisposition to depressive-like behavior and in mice from parental nondepressive CBA strain. It was shown that chronic alcoholization results in a reduction of the BDNF level in the hippocampus and an increase in the amount of TrkB and p75 receptors in the frontal cortex of nondepressive CBA mice. At the same time, the long-term alcoholization of depressive ASC mice results in an increase of the proBDNF level in the frontal cortex and a reduction in the p75 protein level in the hippocampus. It has also been shown that, in depressive ASC mice, proBDNF and BDNF levels are significantly lower in the hippocampus and the frontal cortex compared with nondepressive CBA strain. However, no significant differences in the expression of genes encoding the studied proteins were observed. Thus, changes in the expression patterns of proBDNF, BDNF, and their receptors under the influence of alcoholization in the depressive ASC strain and nondepressive CBA strain mice are different.

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Abbreviations

5-HT:

serotonin

BDNF:

brain-derived neurotrophic factor

proBDNF:

pro-brain-derived neurotrophic factor (BDNF precursor)

TrkB receptor:

tropomyosin receptor kinase B, receptor that mediates the influence of BDNF on neurons

p75 receptor:

receptor that mediates the influence of proBDNF on neurons

rPolII (RNA polymerase II):

DNAdependent RNA polymerase II

RT:

reverse transcription

PCR:

polymerase chain reaction

References

  1. Barde Y.A. 1990. The nerve growth factor family. Prog. Growth Factor Res. 2, 237–248.

    Article  CAS  PubMed  Google Scholar 

  2. Pittenger C., Duman R.S. 2008. Stress, depression, and neuroplasticity: A convergence of mechanisms. Neuropsychopharmacology. 33, 88–109.

    Article  CAS  PubMed  Google Scholar 

  3. Schmidt H.D., Banasr M., Duman R.S. 2008. Future antidepressant targets: Neurotrophic factors and related signaling cascades. Drug Discov. Today Ther. Strateg. 5, 151–156.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ichim G., Tauszig-Delamasure S., Mehlen P. 2012. Neurotrophins and cell death. Exp. Cell Res. 318, 1221–1228.

    Article  CAS  PubMed  Google Scholar 

  5. Hensler J.G., Ladenheim E.E., Lyons W.E. 2003. Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/–) mice. J. Neurochem. 85, 1139–1147.

    Article  CAS  PubMed  Google Scholar 

  6. Sakai R., Ukai W., Sohma H., Hashimoto E., Yamamoto M., Ikeda H., Saito T. 2005. Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells. J. Neural Transm. 112, 1005–1013.

    Article  CAS  PubMed  Google Scholar 

  7. Xu R., Duan S.R., Zhao J.W., Wang C.Y. 2015. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence. Braz. J. Med. Biol. Res. 48, 703–710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ge Y., Belcher S.M., Light K.E. 2004. Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor isoforms occur within hours of ethanol administration to 4-day-old rat pups. Brain Res. Dev. Brain Res. 151, 99–109.

    Article  CAS  PubMed  Google Scholar 

  9. 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, 8285–8295.

    Article  CAS  PubMed  Google Scholar 

  10. Badshah H., Ali T., Ahmad A., Kim M.J., Abid N.B., Shah S.A., Yoon G.H., Lee H.Y., Kim M.O. 2015. Cotreatment with anthocyanins and vitamin C ameliorates ethanol-induced neurodegeneration via modulation of GABAB receptor signaling in the adult rat brain. CNS Neurol. Disord. Drug Targets. 14 (6), 791–803.

    Article  CAS  PubMed  Google Scholar 

  11. Flora S.J., Gautam P., Kushwaha P. 2012. Lead and ethanol co-exposure lead to blood oxidative stress and subsequent neuronal apoptosis in rats. Alcohol Alcoholism. 47, 92–101.

    Article  CAS  PubMed  Google Scholar 

  12. Galecki P., Talarowska M., Anderson G., Berk M., Maes M. 2015. Mechanisms underlying neurocognitive dysfunctions in recurrent major depression. Med. Sci. Monit. 21, 1535–1547.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Catena-Dell’Osso M., Bellantuono C., Consoli G., Baroni S., Rotella F., Marazziti D. 2011. Inflammatory and neurodegenerative pathways in depression: A new avenue for antidepressant development–Curr. Med. Chem. 18, 245–255.

    Google Scholar 

  14. Holleran K.M., Wilson H.H., Fetterly T.L., Bluett R.J., Centanni S.W., Gilfarb R.A., Rocco L.E., Patel S., Winder D.G. 2016. Ketamine and MAG lipase inhibitor- dependent reversal of evolving depressive-like behavior during forced abstinence from alcohol drinking. Neuropsychopharmacology. 41, 2062–2071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Briones T.L., Woods J. 2013. Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis. Neuroscience. 254, 324–334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hashimoto E., Tayama M., Ishikawa H., Yamamoto M., Saito T. 2015. Influence of comorbid alcohol use disorder on treatment response of depressive patients. J. Neural Transm. (Vienna). 122, 301–306.

    Article  CAS  PubMed  Google Scholar 

  17. Vasudeva R.K., Hobby A.R., Kirby L.G. 2015. Ethanol consumption in the Sprague-Dawley rat increases sensitivity of the dorsal raphe nucleus to 5,7-dihydroxytryptamine. Behav. Brain Res. 295, 35–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bazovkina D.V., Tsybko A.S., Filimonova E.A., Il’chibaeva T.V., Naumenko V.S 2016. Influence of chronic alcohol treatment on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes in the mouse brain: Role of the C1473G polymorphism in the gene encoding tryptophan hydroxylase2. Mol. Biol. (Moscow). 50 (2), 262–269.

    Article  CAS  Google Scholar 

  19. Kondaurova E.M., Bazovkina D.V., Kulikov A.V., Popova N.K. 2006. Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice. Genes Brain Behav. 5, 596–601.

    Article  CAS  PubMed  Google Scholar 

  20. Bazovkina D.V., Kulikov A.V., Kondaurova E.M., Popova N.K 2005. Selection for the predisposition to catalelepsy enhances depressive-like traits in mice. Russ. J. Genet. 41 (9), 1002–1007.

    Article  CAS  Google Scholar 

  21. Alperina E.L., Kulikov A.V., Popova N.K., Idova G.V. 2007. Immnune response in mice of a new strain ASC (antidepressants sensitive catalepsy). Bull. Exp. Biol. Med. 144 (2), 221–223.

    Article  CAS  PubMed  Google Scholar 

  22. Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., Popova N.K. 2012. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 214, 59–67.

    Article  CAS  PubMed  Google Scholar 

  23. Bazovkina D.V., Lichman D.V., Kulikov A.V. 2015. The C1473G polymorphism in the tryptophan hydroxylase-2 gene:involvement in ethanol-related behavior in mice. Neurosci. Lett. 589, 79–82.

    Article  CAS  PubMed  Google Scholar 

  24. Farook J.M., Morrell D.J., Lewis B., Littleton J.M., Barron S. 2007. Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster mice. Alcohol. Alcohol. 42, 296–300.

    Article  CAS  PubMed  Google Scholar 

  25. Gurkovskaya O.V., Leonard S.T., Lewis P.B., Winsauer P.J. 2009. Effects of pregnanolone and dehydroepiandrosterone on ethanol intake in rats administered ethanol or saline during adolescence. Alcohol. Clin. Exp. Res. 33, 1252–1264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hedlund L., Wahlstrom G. 2000. Forced ethanol treatment stimulates and inhibits ethanol intake in a rat model of alcoholism. Alcohol Alcoholism. 35, 446–451.

    Article  CAS  PubMed  Google Scholar 

  27. Zhao R.J., Yoon S.S., Lee B.H., Kwon Y.K., Kim K.J., Shim I., Choi K.H., Kim M.R., Golden G.T., Yang C.H. 2006. Acupuncture normalizes the release of accumbal dopamine during the withdrawal period and after the ethanol challenge in chronic ethanol-treated rats. Neurosci. Lett. 395, 28–32.

    Article  CAS  PubMed  Google Scholar 

  28. Kulikov A.V., Naumenko V.S., Voronova I.P., Tikhonova M.A., Popova N.K. 2005. Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an external standard. J. Neurosci. Methods. 141, 97–101.

    Article  CAS  PubMed  Google Scholar 

  29. Naumenko V.S., Osipova D.V., Kostina E.V., Kulikov A.V. 2008. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Methods. 170, 197–203.

    Article  CAS  PubMed  Google Scholar 

  30. Naumenko V.S., Kulikov A.V. 2006. Quantitative assay of 5-HT1A receptor gene expression in the brain. Mol. Biol. (Moscow). 40 (1), 30–36.

    Article  CAS  Google Scholar 

  31. Tikhonova M.A., Kulikov A.V., Bazovkina D.V., Kulikova E.A., Tsybko A.S., Bazhenova E.Y., Naumenko V.S., Akulov A.E., Moshkin M.P., Popova N.K. 2013. Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response. Behav. Brain Res. 243, 53–60.

    Article  PubMed  Google Scholar 

  32. Baek J.K., Heaton M.B., Walker D.W. 1996. Up-regulation of high-affinity neurotrophin receptor, trk B-like protein on western blots of rat cortex after chronic ethanol treatment. Brain Res. Mol. Brain Res. 40, 161–164.

    Article  CAS  PubMed  Google Scholar 

  33. Tapia-Arancibia L., Rage F., Givalois L., Dingeon P., Arancibia S., Beauge F. 2001. Effects of alcohol on brain-derived neurotrophic factor mRNA expression in discrete regions of the rat hippocampus and hypothalamus. J. Neurosci. Res. 63, 200–208.

    Article  CAS  PubMed  Google Scholar 

  34. Miller R., King M.A., Heaton M.B., Walker D.W. 2002. The effects of chronic ethanol consumption on neurotrophins and their receptors in the rat hippocampus and basal forebrain. Brain Res. 950, 137–147.

    Article  CAS  PubMed  Google Scholar 

  35. Okamoto H., Miki T., Lee K.Y., Yokoyama T., Kuma H., Gu H., Li H.P., Matsumoto Y., Yamaoka I., Fusumada K., Imagawa T., Wang Z.Y., Nakamura Y., Takeuchi Y. 2006. Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus. Okajimas Folia Anat Jpn. 83, 1–6.

    Article  CAS  PubMed  Google Scholar 

  36. Frank L., Wiegand S.J., Siuciak J.A., Lindsay R.M., Rudge J.S. 1997. Effects of BDNF infusion on the regulation of TrkB protein and message in adult rat brain. Exp. Neurol. 145, 62–70.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to V. S. Naumenko.

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Original Russian Text © D.V. Bazovkina, E.M. Kondaurova, A.S. Tsybko, A.I. Kovetskaya, T.V. Ilchibaeva, V.S. Naumenko, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 4, pp. 647–655.

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Bazovkina, D.V., Kondaurova, E.M., Tsybko, A.S. et al. The effects of chronic alcoholization on the expression of brain-derived neurotrophic factor and its receptors in the brains of mice genetically predisposed to depressive-like behavior. Mol Biol 51, 571–578 (2017). https://doi.org/10.1134/S0026893317040057

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  • DOI: https://doi.org/10.1134/S0026893317040057

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