Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice

Cells

Evgeny L. Zavjalov¹  Chih-Li Lin²  Nataliya P. Bgatova³  Maria A. Tikhonova⁴  Nina I. Dubrovina⁴  Natalya V. Goncharova⁴  Marina V. Ovsyukova⁴  Tatiana A. Korolenko⁴  Tamara G. Amstislavskaya⁴  Michael V. Tenditnik⁴  Alexander B. Pupyshev⁴  Anna A. Akopyan⁴ 

[1] Federal Research Center “Institute of Cytology and Genetics”, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;Scientific Research Institute of Clinical and Experimental Lymphology—branch of the Federal Research Center “Institute of Cytology and Genetics”, Timakova St. 2, 630117 Novosibirsk, Russia;Scientific Research Institute of Neurosciences and Medicine, Timakova St. 4, 630117 Novosibirsk, Russia;

关键词: leptin-deficient db/db mice;    trehalose;    autophagy;    behavior;    memory;    obesity;   

DOI  :  10.3390/cells10102557

来源: DOAJ

【 摘 要 】

Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice). A 2% trehalose solution was administered as drinking water during 24 days of the experiment. Expressions of markers of autophagy (LC3-II), neuroinflammation (IBA1), redox state (NOS), and neuronal density (NeuN) in the brain were assessed by immunohistochemical analysis. For behavioral phenotyping, the open field, elevated plus-maze, tail suspension, pre-pulse inhibition, and passive avoidance tests were used. Trehalose caused a slight reduction in increased blood glucose concentration, considerable autophagy activation, and a decrease in the neuroinflammatory response in the brain along with improvements of exploration, locomotor activity, anxiety, depressive-like behavior, and fear learning and memory in db/db mice. Trehalose exerted some beneficial peripheral and systemic effects and partially reversed behavioral alterations in db/db mice. Thus, trehalose as an inducer of mTOR-independent autophagy is effective at alleviating neuronal and behavioral disturbances accompanying experimental diabetes.

【 授权许可】

Unknown