DOI:https://doi.org/10.22263/2312-4156.2017.4.37
Belyaeva L.E., Fedchenko A.N., Lazuko S.S., Ligetskaya I.V., Shemet Y.N.
Resveratrol prevents the disturbances in the behavior of rats which have undergone prenatal stress
Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus
Vestnik VGMU. 2017;16(4):37-47.
Abstract.
Objectives. To investigate the influence of resveratrol on the behavior, motor-coordination functions and also pain sensitivity of rats born from mothers which have undergone chronic stress during their pregnancy.
Material and methods. The experiments were carried out on 32 mongrel pregnant Rattus Muridae rats subdivided into the groups «control» (n=16) and «stress» (n=16). To reproduce chronic unpredictable stress these rats were deprived of food during one day with the provision of free access to water on the 2nd, the 9th and the 16th days of pregnancy; they were fixed for 20 minutes in a vertical position in the plastic box filled with water (t=23±2°C) to the neck level on the 4th and the 11th days; the imitation of a predator presence (contact with Felis excrements during one day) was performed on the 6th and the 13th days of pregnancy. In each group there was a subgroup of animals (n=8) receiving resveratrol (10 mg/kg) in the solution of 0,5% carboxymethylcellulose via oral gavage daily and a subgroup of rats (n=8) receiving the equivalent volume of 0,5% carboxymethylcellulose solution alone during the whole period of pregnancy. The offspring’s behavior at the age of 1 month and 3 months was studied in the «open field» test, their physical endurance and pain sensitivity were investigated as well.
Results. Under the influence of resveratrol, administered to pregnant rats during chronic stress, the reduced motor activity of their offspring increased and their anxiety decreased. Resveratrol given to pregnant rats during stress contributed to the reduction of hypersensitivity to thermal stimuli causing pain and the restoration of the damaged motor-coordination functions in their offspring. The effects of the resveratrol administration to pregnant rats were stable, as they persisted in their offspring up to the age of 3 months.
Conclusions. The administration of resveratrol to pregnant rats during chronic stress prevents the impairment of their offspring behavior.
Key words: resveratrol, prenatal stress, «open field» test, algesthesia, motor-coordination functions.
References
1. Belyaeva LE, Fedchenko AN, Lazuko SS, Ligetskaya IV. Chronic unpredictable stress at pregnant rats and health of their posterity. Ros Fiziol Zhurn im IM Sechenova. 2016;102(7):852-63. (In Russ.)
2. Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J. Bioactive compounds and antioxidant activity in different types of berries. Int J Mol Sci. 2015 Oct;16(10):24673-706. doi: http://dx.doi.org/10.3390/ijms161024673
3. Dohadwala MM, Vita JA. Grapes and cardiovascular disease. J Nutr. 2009 Sep;139(9):1788S-93S. doi: http://dx.doi.org/10.3945/jn.109.107474
4. Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, et al. Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid Med Cell Longev. 2015;2015:837042. doi: http://dx.doi.org/10.1155/2015/837042
5. Xia N, Förstermann U, Li H. Resveratrol and endothelial nitric oxide. Molecules. 2014 Oct;19(10):16102-21. doi: http://dx.doi.org/10.3390/molecules191016102
6. Palomera-Ávalos V, Griñán-Ferré C, Izquierdo V, Camins A, Sanfeliu C, Pallàs M. Metabolic stress induces cognitive disturbances and inflammation in aged mice: protective role of resveratrol. Rejuvenation Res. 2017 Jun;20(3):202-217. doi: http://dx.doi.org/10.1089/rej.2016.1885
7. Dong E, Dzitoyeva SG, Matrisciano F, Tueting P, Grayson DR, Guidotti A. Brain-derived neurotrophic factor epigenetic modifications associated with schizophrenia-like phenotype induced by prenatal stress in mice. Biol Psychiatry. 2015 Mar;77(6):589-96. doi: http://dx.doi.org/10.1016/j.biopsych.2014.08.012
8. Louey S, Thornburg KL. The prenatal environment and later cardiovascular disease. Early Hum Dev. 2005 Sep;81(9):745-51.
9. Das S, Lin HS, Ho PC, Ng KY. The impact of aqueous solubility and dose on the pharmacokinetic profiles of resveratrol. Pharm Res. 2008 Nov;25(11):2593-600. doi: http://dx.doi.org/10.1007/s11095-008-9677-1
10. Samardzić J, Jadzić D, Radovanović M, Jancić J, Obradović DI, Gojković-Bukarica L, et al. The effects of resveratrol on rat behaviour in the forced swim test. Sap Arh Celok Lek. 2013 Sep-Oct;141(9-10):582-5.
11. Liu S, Li T, Liu H, Wang X, Bo S, Xie Y, Bai X, et al. Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex. Behav Brain Res. 2016 Apr;302:191-9. doi: http://dx.doi.org/10.1016/j.bbr.2016.01.037
12. Yazir Y, Utkan T, Gacar N, Aricioglu F. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress. Physiol Behav. 2015 Jan;138:297-304. doi: http://dx.doi.org/10.1016/j.physbeh.2014.10.010
13. Wang X, Xie Y, Zhang T, Bo S, Bai X, Liu H, et al. Resveratrol reverses chronic restraint stress-induced depression-like behaviour: involvement of BDNF level, ERK phosphorylation and expression of Bcl-2 and Bax in rats. Brain Res Bull. 2016 Jul;125:134-43. doi: http://dx.doi.org/10.1016/j.brainresbull.2016.06.014
14. Arteaga O, Revuelta M, Urigüen L, Álvarez A, Montalvo H, Hilario E. Pretreatment with resveratrol prevents neuronal injury and cognitive deficits induced by perinatal hypoxia-ischemia in rats. PLoS One. 2015 Nov;10(11):e0142424. doi: http://dx.doi.org/10.1371/journal.pone.0142424
15. Isac S, Panaitescu AM, Spataru A, Iesanu M, Totan A, Udriste A, et al. Trans-resveratrol enriched maternal diet protects the immature hippocampus from perinatal asphyxia in rats. Neurosci Lett. 2017 Jul;653:308-313. doi: http://dx.doi.org/10.1016/j.neulet.2017.06.003
16. Wang G, Hu Z, Song X, Cui Q, Fu Q, Jia R, et al. Analgesic and anti-Inflammatory activities of resveratrol through classic models in mice and rats. Evid Based Complement Alternat Med. 2017;2017:5197567. doi: http://dx.doi.org/10.1155/2017/5197567
17. Takeda M, Takehana S, Sekiguchi K, Kubota Y, Shimazu Y. Modulatory mechanism of nociceptive neuronal activity by dietary constituent resveratrol. Int J Mol Sci. 2016 Oct;17(10). doi: http://dx.doi.org/10.3390/ijms17101702
Information about authors:
Belyaeva L.E. – Candidate of Medical Sciences, associate professor, head of the Chair of Pathologic Physiology, Vitebsk State Order of Peoples’ Friendship Medical University;
Fedchenko A.N. – Master of Medical Sciences, teacher of the Chair of Pathologic Physiology, Vitebsk State Order of Peoples’ Friendship Medical University;
Lazuko S.S. – Candidate of Biological Sciences, associate professor, head of the Chair of Normal Physiology, Vitebsk State Order of Peoples’ Friendship Medical University;
Ligetskaya I.V. – Master of Biological Sciences, teacher of the Chair of Pathologic Physiology, Vitebsk State Order of Peoples’ Friendship Medical University;
Shemet Y.N. – the fourth-year medical student, Vitebsk State Order of Peoples’ Friendship Medical University.
Correspondence address: Republic of Belarus, 210023, Vitebsk, 27 Frunze ave., Vitebsk State Order of Peoples’ Friendship Medical University, Chair of Pathologic Physiology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Lyudmila E. Belyaeva.
