Molecular expression of insulin signal transduction components in brain cells in an experimental model of Alzheimer’s disease

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Abstract

Introduction. The risk of Alzheimer’s disease (AD) is increased with cerebral insulin resistance, which may be caused by the impaired function of the cerebrovascular system, and may also have a direct effect on β-amyloid aggregation and Tau protein phosphorylation.

Aim. To study the molecular expression of insulin signal transduction components (IRS1, GSK3B and PKC) in the brain cells in an experimental model of AD.

Materials and methods. Experiments were conducted on 4-month-old C57BL/6 and B6.129S6-Nlrp3tm1Bhk/JJ male mice (NLRP3 knockout mice) with 5 animals in each group. AD was modelled in the experimental group of mice by administering β-amyloid; mice in the control group received sham surgery. IRS1, GSK3B and PKC expression in the amygdala was studied using immunohistochemistry methods.

Results. The C57BL/6 mice with AD had reduced IRS1 expression compared with the mice who received sham surgery (0.62±0.13 and 0.89±0.17; р=0.045), while the β-amyloid did not produce the same result in NLRP3 knockout mice. GSK3B expression was increased in C57BL/6 mice with AD (0.60±0.12) when compared with both the control group (0.20±0.02; p<0.0001) and the NLRP3 knockout mice with AD (0.27±0.08; p<0.0001). PKC expression in C57BL/6 mice with AD was reduced (0.52±0.14) when compared with the NLRP3 knockout mice with AD (0.89±0.18; p<0.05) and the control group (0.84±0.12; p<0.05).

Conclusion. The development of Alzheimer type-neurodegeneration is accompanied by disruptions in IRS1 and GSK3B expression, which is associated with impaired signal transmission along the PKC pathway. The suppression of neuroinflammation through NLRP3 inflammasome deletion has a protective effect in AD.

 

About the authors

Yana V. Gorina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Author for correspondence.
Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Yuliya K. Komleva

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Olga L. Lopatina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Anatolii I. Chernykh

Krasnoyarsk City Hospital No. 20 named after I.S. Berzon

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Alla B. Salmina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

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