Effect of Trehalose on Autophagy Gene Transcription and Ultrastructural Changes in Neurons and Brain Glia Cells of 5-Month-Old db/db Mice Modelling Type 2 Diabetes with the Development of Neurodegeneration

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Abstract

Type 2 diabetes is associated with the formation of features of Alzheimer's disease (AD). A common mechanism appears to be the impairment of autophagy, making its stimulation a potential target for AD treatment. A good opportunity to study the correction of diabetes and neurodegeneration is provided by db/db mice, a model of diabetes and obesity that develop signs of AD with age. In our previous work, we found that db/db mice are amenable to treatment with the disaccharide trehalose, which activates autophagy via an mTOR-independent pathway. In 3-month-old mice, trehalose reduced obesity, attenuated hyperglycaemia, significantly activated autophagy in the brain, weakened neuroinflammation and oxidative stress, and restored cognitive impairment. It remains unclear to what extent the therapeutic effect of trehalose depends on the age of mice and on the activation of autophagy gene transcription and ultrastructural changes in neurons and glia cells. The therapeutic effect of treatment with 3% trehalose in drinking was investigated on 5-month-old db/db mice. Trehalose did not induce a significant decrease in the body mass or blood glucose and cholesterol levels but it decreased the expression of the insulin receptor gene Insr. There was a visual increase in the lipofuscin levels in cortical neurons and glial cells, while trehalose did not attenuate the accumulation of the marker. Thus, a differential effect of trehalose was obtained for 5-month-old db/db mice, consisting in the absence of activation of autophagy gene transcription or attenuation of lipofuscin accumulation. Apparently, the therapeutic effect of trehalose on the disturbances in db/db line mice decreases with age and becomes ineffective at 5 months of age.

About the authors

T. A. Korolenko

Scientific Research Institute of Neurosciences and Medicine

Email: box2023atiana@mail.ru
Novosibirsk, Russia

A. B. Pupyshev

Scientific Research Institute of Neurosciences and Medicine

Email: puryshevab@neuronn.ru
Novosibirsk, Russia

V. M. Belichenko

Scientific Research Institute of Neurosciences and Medicine

Novosibirsk, Russia

N. P. Bagatova

Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

M. V. Tenditnik

Scientific Research Institute of Neurosciences and Medicine

Novosibirsk, Russia

L. A. Fedoseeva

Scientific Research Institute of Neurosciences and Medicine; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

N. V. Goncharova

Scientific Research Institute of Neurosciences and Medicine

Novosibirsk, Russia

M. V. Ovsyukova

Scientific Research Institute of Neurosciences and Medicine

Novosibirsk, Russia

E. T. Korolenko

University of Western Canada

Vancouver, British Columbia, Canada

E. L. Zavjalov

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk Russia

M. A. Tikhonova

Scientific Research Institute of Neurosciences and Medicine

Novosibirsk, Russia

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