Journal
CELLS
Volume 10, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/cells10102557
Keywords
leptin-deficient db/db mice; trehalose; autophagy; behavior; memory; obesity; neurodegeneration
Categories
Funding
- Russian Government for basic scientific research of the Scientific Research Institute of Neurosciences and Medicine [AAAA-A21-121011990039-2, 2021-2025]
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Treating diabetic db/db mice with trehalose, an autophagy inducer, led to reduced blood glucose levels, increased autophagy, decreased neuroinflammation, and improved behavior. This suggests that trehalose has potential therapeutic effects in alleviating neuronal and behavioral disturbances associated with diabetes.
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.
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