In recent years, a direction studying the relationship between the state of intestinal microbiota and brain functioning, the so-called “microbiome-gut-brain” axis, has been actively developing. It has been shown that the gut microbiota can influence brain function through various mechanisms such as synthesis of neurotransmitters, regulation of inflammation and modulation of the immune system. Probiotics, especially probiotic microbial consortia (PMCs) capable of modulating the composition of the microbiota, are considered as potential correctors of not only metabolic but also behavioral disorders. They produce anxiolytic and antidepressant effects characterized by positive changes in emotional, cognitive, systemic and nervous spheres. However, studies aimed at evaluating behavioral responses in diabetes under conditions of probiotic administration remain insufficient. Therefore, the aim of this work was to study the effect of probiotic microbial consortium on behavioral responses of alloxan-induced diabetic rats in the infrared actimeter test. The total sample consisted of 30 healthy rats, weighing 280–330 g, divided into 3 experimental groups of 10 animals each. The animals of the first group (K) were kept in standard vivarium conditions and served as biological control. The rats of the second (Al) and third (Al+Pb) groups were modeled diabetes mellitus by intraperitoneal injection of alloxan (mesoxalylurea, C4O4H2N2×H₂O, Diaem Company, Russia) at a dosage of 100 mg/kg for three days. Alloxan is a relatively inexpensive and readily available chemical compound. Diabetes develops within a few days after its administration, which allows for rapid research. To determine the occurrence of diabetes during the experiment, the concentration of glucose in blood taken from the tail incision of rats was monitored using an “iCheck” glucometer. On the 10th day, the animals of the third group (Al+Pb) were intragastrically administered 1% PMC solution by 3 ml for the next 21 days. Animals of the first (K) and second (Al) groups were administered an equivalent volume of drinking water. The results of the study demonstrate a pronounced negative effect of alloxan-induced diabetes mellitus on the behavioral activity of rats, which is manifested by a decrease in total activity, a reduction in the distance covered, a decrease in the average speed of movement and an increase in resting time. These changes indicate the development of general hypodynamia associated with a complex of metabolic and neurological disorders typical of the diabetic state. At the same time, a steady and statistically significant decrease in all key behavioral indices is especially pronounced on the 14th day of observation, when the greatest drop in both total activity (by 270 units), as well as in the distance traveled (by 513.95 units) and average speed (by 3.15 cm/s) was recorded. This may indicate a peak of destructive metabolic disturbances associated with prolonged energy deficit and increasing neuroinflammation. Diabetic neuropathy, hyperglycemia and oxidative stress, increase at this stage, which is reflected in the behavior of the animals. In the Al+Pb group, where rats were administered PMC against alloxan diabetes on the background of 14 days on the contrary, a partial recovery of behavioral reactions was observed: total activity, distance covered and average speed approached the values of the control group and significantly exceeded the similar parameters of the Al group. This may indicate a positive effect of PMC on the metabolic state of animals due to the normalization of intestinal microbiota and reduction of inflammation at the level of the axis “microbiome-intestine-brain”. It is known that probiotics can reduce the level of systemic inflammation, oxidative stress and increase tissue sensitivity to insulin. Against the background of alloxan diabetes, administration of PMC can contribute to the restoration of energy metabolism and reduce the neurotoxic effects of chronic hyperglycemia, which, in turn, is expressed in the increase in motor activity of animals. However, on the 21st day of the experiment, a secondary decrease in all behavioral parameters is observed, although they do not reach the values recorded in animals of the Al group. The possible reason may be the depletion of compensatory mechanisms. Thus, administration of PMC has a modulating and partially restorative effect on behavioral responses of alloxan-induced diabetic rats, contributing to the reduction of the degree of motor depression characteristic of the diabetic state, and can be considered as a promising direction in adjuvant therapy of diabetes mellitus aimed at the correction of behavioral disorders.
alloxan, diabetes mellitus, probiotic microbial consortium, motor activity, rats
1. Dedov I. I. Saharnyy diabet / I. I. Dedov, M. V. Shestakova, A. Yu. Mayorov, M. Sh. Shamhalova // Saharnyy diabet. – 2020. – T. 23. – S. 42–114. doi:https://doi.org/10.14341/DM12505
2. Luneva I. E. Kognitivnye narusheniya u bol'nyh saharnym diabetom. / Luneva I. E., Suponeva N. A. // Effektivnaya farmakoterapiya. – 2022. – 18 (10). – S. 38–44.
3. Yusupova D. G. Osobennosti klinicheskoy diagnostiki emocional'nyh i kognitivnyh narusheniy u pacientov s saharnym diabetom. / Yusupova D. G., Suponeva N. A. //Effektivnaya farmakoterapiya.
4. Bourassa M. W. Neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? / M. W. Bourassa, I. Alim, S. J. Bultman [et al.] // Butyrate Neurosci. Lett. – 2016. – V. 625. – P. 56–63.
5. Mingxue Gao. Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression / Mingxue Gao, Jizhi Wang, Penghong Liu, Hongwei Tu, Ruiyu Zhang,
6. Ivashkin V. T. Psihobioticheskie effekty probiotikov i prebiotikov. / V. T. Ivashkin, K. V. Ivashkin // Ros. zhurn. gastroenterol., gepatol., koloproktol. – 2018. – № 28 (1) – S. 4–12.
7. Pal'chikova N. A. Gormonal'no-biohimicheskie osobennosti alloksanovoy i streptozotocinovoy modeley eksperimental'nogo diabeta. / Pal'chikova N. A., Kuznecova N. V., Kuz'minova O. I.
8. Carlos Alberto Yasin Wayhs. Diabetic encephalopathy-related depression: experimental evidence that insulin and clonazepam restore antioxidant status in rat brain / Carlos Alberto Yasin Wayhs,
9. Danilova I. G. Sposob modelirovaniya alloksanovogo diabeta / I. G. Danilova, I. F. Gette: Patent na izobretenie № 2534411; zayavl. 27.11.2014; opubl. 27.11.2014. – Byul. № 33.
10. Saltiel A. R. Insulin signaling in health and disease / Saltiel A. R. // J Clin Invest – 2021. – 131(1). – e142241. doi:https://doi.org/10.1172/JCI142241.
11. Korneeva A. V. Izmenenie povedencheskih reakciy u krys s saharnym diabetom na fone ishemii mozga / A. V. Korneeva, G. I. Gorohova, A. A. Fudashkin, V. A. Lemeshenko, E. G. Filipchenko
12. Miroshnichenko I. Yu. Vliyanie reamberina i al'fa-lipoevoy kisloty na rasstroystva povedeniya i metabolizma pri eksperimental'nom saharnom diabete : dissertaciya kand.med.nauk. : 14.03.06
13. Volchegorskiy I. A. Antioksidanty pri eksperimental'nom saharnom diabete. / Volchegorskiy I. A., Rassohina L. M., Miroshnichenko I. Yu. // Problemy Endokrinologii. – 2008. – 54(5). – S. 43–49.
14. Chervinec V. M. Vliyanie kishechnoy mikrobioty na razvitie saharnogo diabeta. / Chervinec V. M., Chervinec Yu. V., Ganzya D. V., Belyaev V. S., Zayceva V. S. // Eksperimental'naya i klinicheskaya
