Protective effect of intranasal insulin on memory impairment in mice exposed to high altitude

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Protective effect of intranasal insulin on memory impairment in mice exposed to high altitude

Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 11

Abstract

Objective To explore the protective effect and mechanism of intranasal administration of insulin on memory impairment in mice exposed to high altitude. Methods Eighty female C57BL / 6 mice were randomly divided into normoxic control (CON) group, high altitude (HH) group, normal saline (NS + HH) group, insulin pretreatment (I + HH) group and insulin therapy (HH + I) group, with 16 mice in each group. After 7 d of continuous nasal feeding of normal saline or insulin 17. 5 μL (i. e., insulin 1. 75 U) in NS + HH group and I + HH group, they were placed in a hypobaric oxygen chamber with HH group and HH + I group at a simulated altitude of 6 000 m for 7 d. During this period, HH + I group was administered 1. 75 U of intranasal insulin every day. The cognitive function of mice was tested by Morris water maze experiment. Oxidative stress, neuronal apoptosis, and changes in synaptic function in hippocampus were observed by hydrogen peroxide (H2O2 ) test kit, malondialdehyde ( MDA) test kit, superoxide dismutase ( SOD) test kit, Western blotting, and Nissl staining. Results ①Compared with CON group, mice in HH group ( P < 0. 01 ) showed obvious memory impairment, and mice in HH + I group significantly improved memory (P < 0. 01); ②Compared with CON group, oxidative stress indexes H2 O2 (P < 0. 05) and MDA (P < 0. 05) of hippocampal region in HH group increased, and the antioxidant index SOD showed a decreasing trend. The oxidative stress indexes were reversed in I + HH group and HH + I group; ③Nissl staining showed that the dissolution of Nissl bodies of neurons in CA1 region was obvious in HH group, and this phenomenon was significantly reduced in I + HH group and HH + I group. A large number of nuclear pyknotic hyperchromatic cells appeared in CA3 region of HH group, and the number of nuclear pyknotic hyperchromatic cells in I + HH group and HH + I group decreased significantly; ④Compared with CON group, the expression of B-cell lymphoma-2 in HH group was significantly reduced (P < 0. 01), and the expression of cleaved caspase-3 was significantly increased (P < 0. 01). The expression of apoptosis-associated proteins was reversed in I + HH group and HH + I group; ⑤Compared with CON group, the expression level of synapsin 1 (Syn-1) in HH group (P < 0. 05) decreased, and the expression of Syn-1 in I + HH group (P < 0. 01) and HH + I group (P < 0. 05) increased significantly. Conclusion Intranasal insulin can prevent and treat memory impairment induced by high altitude environment through alleviating hippocampal oxidative stress damage, reducing neuronal apoptosis, and improving synaptic function.

Authors and Affiliations

CHEN Siyu, LENG Yujie, ZHANG Ming, LIN Lu, YUAN Libang, GONG Gu

Keywords

hypobaric hypoxia; insulin; intranasal administration; learning and memory; oxidative stress; apoptosis; synapsin 1

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EP ID EP724133
DOI -
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