Diabetes Type 2 as a Risk Factor of Neurodegeneration Development and Cognitive Impairment in db/db Mice

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Tatyana A. Korolenko¹, Nina I. Dubrovina², Marina V. Ovsyukova³, Natalya P. Bgatova⁴, Chih-Li Lin⁵, Alexander B. Pupyshev⁶, Evgeniy L. Zavjalov⁷, Elena V. Anufrienko Scientific Research Institute^8
1Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, t.a.korolenko@physiol.ru
²Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, dubrov@physiol.ru
³Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, ovsyukovamv@physiol.ru
⁴Federal Research Center “ICG SB RAS”, Novosibirsk, Russia, n.bgatova@ngs.ru
⁵Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, dll@csmu.edu.tw
⁶Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, apupyshev@physiol.ru
⁷Federal Research Center “ICG SB RAS”, Novosibirsk, Russia, zavjalov@bionet.nsc.ru
⁸Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, anufrienko@ngs.ru

Diabetes T2 with insulin resistance is a serious disease all over the world with a tendency to steady increase the number of cases and a risk factor of neurodegenerative diseases development, among them firstly Alzheimer’s disease. The aim of this study was to investigate behavior and general characteristic of genetic model of diabetes T2 mice db/db, trying to reveal beginning of development early symptoms of neurodegeneration development and characteristic of symptoms of diabetes T2 during treatment by liraglutide or autophagy inducer trehalose. Mice age was 3 and 5 months. Db/db mice had an increase in body weight, which progressed with age, a decrease in brain mass. Blood glucose levels were increased in db/db mice. Treatment with trehalose or liraglutide reduces its level. Db/db mice were characterized by decrease of overall orientation-exploratory and locomotor activities, increase in anxiety in the open field test. Liraglutide treatment showed positive change in open field test in db/db mice. Passive avoidance test revealed significant decrease in motivation, locomotor and exploratory activity, decreased learning in db/db mice. Db/db mice of both ages were characterized by an increase in the relative number of PMN and monocytes and a decrease in the number of lymphocytes, indicating an inflammatory response. Treatment with trehalose or liraglutide restored these indicators. Thus, the identified behavioral changes in db/db mice reflected the development of neurodegeneration signs. Some positive effects of liraglutide on behavioral processes have been shown. Trehalose and liraglutide reduced blood glucose levels and the severity of the inflammatory response.