Features of the Behavior and Activity of Blood Enzymes of the Offspring of Rats Conceived by Their Father Under the Influence of Alcohol

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Abstract

Quite often, conception of a child occurs after consuming small doses of alcohol. However, the effect of this factor on offspring has not been studied at all. The aim of this study was to study the level of motor activity, anxiety-like and depressive-like behavior, sensitivity to the analgesic effect of ethanol, as well as the activity of the enzymes DPP-IV, PEP and ADG in the blood of rats whose fathers received ethanol immediately before mating. As a result of the experiments conducted, it was found that males conceived by fathers who were intoxicated have significant differences in behavior compared to control animals. Thus, motor activity in rats conceived by males under the influence of alcohol was 2-2.5 times less intense, they decreased the severity of anxiety-like and depressive-like behavior. In such animals, the activity of DPP-IV and ADG was increased and the activity of PEP in the blood was reduced. In rats conceived by fathers under the influence of alcohol, the analgesic effect of ethanol decreased, and there was also a decrease in the reaction of ADG, DPP-IV and PEP to ethanol administration. It is assumed that a single use of ethanol by male rats immediately before mating leads to a decrease in the methylation of paternal inherited genes in offspring. As a result, the activity of a number of enzymes may change, which leads to a change in the balance of neuropeptides involved in formation of animal behavior.

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S. K. Sudakov

Anokhin Research Institute

Author for correspondence.
Email: s-sudakov@mail.ru
Russian Federation, 125315, Moscow

N. G. Bogdanova

Anokhin Research Institute

Email: s-sudakov@mail.ru
Russian Federation, 125315, Moscow

G. A. Nazarova

Anokhin Research Institute

Email: s-sudakov@mail.ru
Russian Federation, 125315, Moscow

N. N. Zolotov

Anokhin Research Institute

Email: s-sudakov@mail.ru
Russian Federation, 125315, Moscow

References

  1. Gilliam, D. M., Stilman, A., Dudek, B. C., and Riley, E. P. (1987) Fetal alcohol effects in long- and short-sleep mice: activity, passive avoidance, and in utero ethanol levels, Neurotoxicol. Teratol., 9, 349-357, https:// doi.org/10.1016/0892-0362(87)90030-4.
  2. Carneiro, L. M., Diógenes, J. P., Vasconcelos, S. M., Aragão, G. F., Noronha, E. C., Gomes, P. B., and Viana, G. S. (2005) Behavioral and neurochemical effects on rat offspring after prenatal exposure to ethanol, Neurotoxicol. Teratol., 27, 585-592, https://doi.org/10.1016/j.ntt.2005.06.006.
  3. Kim, P., Choi, C. S., Park, J. H., Joo, S. H., Kim, S. Y., Ko, H. M., Kim, K. C., Jeon, S. J., Park, S. H., Han, S. H., Ryu, J. H., Cheong, J. H., Han, J. Y., Ko, K. N., and Shin, C. Y. (2014) Chronic exposure to ethanol of male mice before mating produces attention deficit hyperactivity disorder-like phenotype along with epigenetic dysregulation of dopamine transporter expression in mouse offspring, J. Neurosci. Res., 92, 658-670, https://doi.org/10.1002/jnr.23275.
  4. Abel, E. L., and Lee, J. A. (1988) Paternal alcohol exposure affects offspring behavior but not body or organ weights in mice, Alcohol. Clin. Exp. Res., 12, 349-355, https://doi.org/10.1111/j.1530-0277.1988.tb00205.x.
  5. Wozniak, D. F., Cicero, T. J., Kettinger, L., and Meyer, E. R. (1991) Paternal alcohol consumption in the rat impairs spatial learning performance in male offspring, Psychopharmacology, 105, 289-302, https://doi.org/10.1007/BF02244324.
  6. Ledig, M., Misslin, R., Vogel, E., Holownia, A., Copin, J. C., and Tholey, G. (1998) Paternal alcohol exposure: developmental and behavioral effects on the offspring of rats, Neuropharmacology, 37, 57-66, https://doi.org/10.1016/S0028-3908(97)00185-8.
  7. Rompala, G. R., Finegersh, A., Slater, M., and Homanics, G. E. (2017) Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background, Alcohol, 60, 169-177, https://doi.org/10.1016/j.alcohol.2016.11.001.
  8. Finegersh, A., and Homanics, G. E. (2014) Paternal alcohol exposure reduces alcohol drinking and increases behavioral sensitivity to alcohol selectively in male offspring, PLoS One, 9, e99078, https://doi.org/10.1371/journal.pone.0099078.
  9. Bielawski, D. M., and Abel, E. L. (1997) Acute treatment of paternal alcohol exposure produces malformations in offspring, Alcohol, 4, 397-401, https://doi.org/10.1016/s0741-8329(97)87951-87957.
  10. Meek, L. R., Myren, K., Sturm, J., and Burau, D. (2007) Acute paternal alcohol use affects offspring development and adult behavior, Physiol. Behav., 91, 154-160, https://doi.org/10.1016/j.physbeh.2007.02.004.
  11. Sharma, A. N., Pise, A., Sharma, J. N., and Shukla, P. (2015) Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats, Metab. Brain Dis., 30, 659-667, https://doi.org/10.1007/s11011-014-9603-7.
  12. Frenssen, F., Croonenberghs, J., Van den Steene, H., and Maes, M. (2015) Prolyl endopeptidase and dipeptidyl peptidase IV are associated with externalizing and aggressive behaviors in normal and autistic adolescents, Life Sci., 136, 157-162, https://doi.org/10.1016/j.lfs.2015.07.003.
  13. Maes, M., Goossens, F., Lin, A., De Meester, I., Van Gastel, A., and Scharpé, S. (1998) Effects of psychological stress on serum prolyl endopeptidase and dipeptidyl peptidase IV activity in humans: higher serum prolyl endopeptidase activity is related to stress-induced anxiety, Psychoneuroendocrinology, 23, 485-495, https:// doi.org/10.1016/s0306-4530(98)00020-1.
  14. Maes, M., Lin, A., Bonaccorso, S., Vandoolaeghe, E., Song, C., Goossens, F., De Meester, I., Degroote, J., Neels, H., Scharpé, S., and Janca, A. (1998) Lower serum activity of prolyl endopeptidase in fibromyalgia is related to severity of depressive symptoms and pressure hyperalgesia, Psychol. Med., 28, 957-965, https://doi.org/10.1017/s0033291798006801.
  15. Maes, M., Lin, A., Bonaccorso, S., Vandoolaeghe, E., Song, C., Goossens, F., De Meester, I., Degroote, J., Neels, H., Scharpé, S., and Janca, A. (1999) Lower activity of serum peptidases in abstinent alcohol-dependent patients, Alcohol, 17, 1-6, https://doi.org/10.1016/s0741-8329(98)00022-6.
  16. Crabb, D. W., Matsumoto, M., Chang, D., and You, M. (2004) Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology, Proc. Nutr. Soc., 63, 49-63, https://doi.org/10.1079/pns2003327.
  17. Mezey, E., Cherrick, G. R., and Holt, P. R. (1968) Serum alcohol dehydrogenase, an indicator of intrahepatic cholestasis, N. Engl. J. Med., 279, 241-248, https://doi.org/10.1056/NEJM196808012790504.
  18. Jin, S., Cinar, R., Hu, X., Lin, Y., Luo, G., Lovinger, D. M., Zhang, Y., and Zhang, L. (2021) Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice, Br. J. Anaesth., 127, 296-309, https:// doi.org/10.1016/j.bja.2021.02.035.
  19. Szuba, M. P., Amsterdam, J. D., Fernando, A., and Winokur, A. (2005). Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression, J. Clin. Psychopharm., 25, 325-330, https://doi.org/10.1097/01.jcp.0000169037.17884.79.
  20. Charli, J.-L., Rodríguez-Rodríguez, A., Hernández-Ortega, K., Cote-Vélez, A, Uribe, R. M., Jaimes-Hoy, L., and Joseph-Bravo, P. (2020) The thyrotropin-releasing hormone-degrading ectoenzyme, a therapeutic target? Front. Pharmacol., 11, 640, https://doi.org/10.3389/fphar.2020.00640.
  21. Золотов Н. Н., Наркевич В. Б., Позднев В. Ф. (1992) О психотропных свойствах ингибиторов пролилэндопептидазы мозга, Докл. Акад. Наук СССР, 322, 624-625.
  22. Guieu, R., Fenouillet, E., Devaux, C., Fajloun, Z., Carrega, L., Sabatier, J. M., Sauze, N., and Marguet, D. (2006) CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity, Behav. Brain Res., 166, 230-235, https://doi.org/10.1016/j.bbr.2005.08.003.
  23. Fichna, J., do-Rego, J-C., Chung, N. N., Lemieux, C., Schiller, P. W., Poels, J., Broeck, J. V., Costentin, J., and Janecka, A. (2007) Synthesis and characterization of potent and selective µ-opioid receptor antagonists, [Dmt1, D-2-Nal4]endomorphin-1 (antanal-1) and [Dmt1, D-2-Nal4]endomorphin-2 (antanal-2), Pharmacol Rev., 59, 88-123.
  24. Wagner, L., Kaestner, F., Wolf, R., Stiller, H., Heiser, U., Manhart, S., Hoffmann, T., Rahfeld, J. U., Demuth, H. U., Rothermundt, M., von Hörsten, S. (2016). Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation, Neuropeptides, 57, 21-34, https://doi.org/10.1016/ j.npep.2016.02.007.
  25. Liang, F., Diao, L., Liu, J., Jiang, N., Zhang, J., Wang, H., Zhou, W., Huang, G., and Ma, D. (2014) Paternal ethanol exposure and behavioral abnormities in offspring: associated alterations in imprinted gene methylation, Neuropharmacology, 81, 126-133, https://doi.org/10.1016/j.neuropharm.2014.01.025.

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2. Fig. 1. Changes in the behaviour of male rats conceived by intoxicated fathers. a - Motor activity (units) in experimental chambers ‘Phenomaster’; b - horizontal motor activity (units. ) in the ‘open field’ test; c - vertical motor activity (stance) in the ‘open field’ test; d - duration of stay in light sleeves of PCL (s); e - duration of immobilisation of rats in the ‘hanging by tail’ test (s). The figures indicate reliable differences from the control (nonparametric Mann-Whitney U-criterion)

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3. Fig. 2. Latent period of paw licking of rats of experimental groups in the hot plate test. * Significant differences between animals injected with saline and ethanol in each offspring group, U = 3.00, p = 0.002176 in the ‘Control’ group; U = 5.50, p = 0.002953 in the ‘Ethanol 0.5 g/kg’ group

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