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Cited by 37Autophagy in Disease and TherapyNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

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

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Korolenko, Tatiana, Dubrovina, Nina, Ovsyukova, Marina, Bgatova, Nataliya, Tenditnik, Michael, Pupyshev, Alexander, Akopyan, Anna, Goncharova, Natalya +4 more·2021·Cells
DOI 10.3390/cells10102557PMC PMC8533743
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Abstract

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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  • Trehalose, spermidine, and resveratrol have been explored for their ability to stimulate autophagy and mitophagy with relative safety.

    “Small molecules such as trehalose, spermidine, and resveratrol have been explored for their ability to stimulate autophagy and mitophagy with relative safety [145, 146].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [145]

    The Discussion (page unavailable) identifies trehalose, spermidine, and resveratrol as compounds associated with restored autophagy that processes dysfunctional mitochondria. The Introduction calls trehalose nontoxic, but the paper does not establish relative safety for spermidine or resveratrol, or specifically show that all three stimulate mitophagy. (LLM, conf=0.87)

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Authors
Korolenko, T., Dubrovina, N., Ovsyukova, M., Bgatova, N., Tenditnik, M., Pupyshev, A., Akopyan, A., Goncharova, N., Lin, C.-L., Zavjalov, E., Tikhonova, M., & Amstislavskaya, T.
Affiliations
  • Scientific Research Institute of Neurosciences and Medicine, Timakova St. 4, 630117 Novosibirsk, Russia
  • Institute of Cytology and Genetics (RU)
  • Chung Shan Medical University (TW)
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-09-27
Volume
10
Issue
10
Pages
2557
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10102557
PMC
PMC8533743
OpenAlex
W3202685486
Cited by
37
References
0
Citations by year
2026: 7 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 9
FWCI
3.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
trehalose, autophagy, db/db mice, type 2 diabetes, neuroinflammation, memory impairment, anxiety-like behavior, depression-like behavior, fear learning, mTOR-independent autophagy, LC3-II, neuronal injury, blood glucose, neuroprotection
MeSH terms
Problem Behavior, Neuroinflammatory Diseases, Animals, Autophagy, Disease Models, Animal, Male, Memory Disorders, Trehalose, Mice

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