Expression of IP3R2 and RYR2 mediated Ca2+ signals in a mouse model of delayed encephalopathy after acute carbon monoxide poisoning

doi:10.12307/2025.246

Abstract

Abstract: BACKGROUND: Ca2+ expression in astrocytes has been found to be closely related to cognitive function, and the Ca2+ signaling pathway regulated by inositol 1,4,5-trisphosphate receptors (IP3R2) and ryanodine receptor (RYR) 2 receptors has become a hot spot in the study of cognitive disorder-related diseases.
OBJECTIVE: To investigate the expression of Ca2+ signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning, and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning.
METHODS: C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group. An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group, and the same amount of air was inhaled in the control group. Behavioral and neuronal changes, astrocyte specific marker glial fibrillary acidic protein, IP3R2, RYR2 receptor and Ca2+ concentration in astrocytes of the two groups were detected using Morris water maze, hematoxylin-eosin staining, western blot, immunofluorescence double labeling and Ca2+ fluorescence probe at 21 days after modeling.
RESULTS AND CONCLUSION: In the Morris water maze, the escape latency of the experimental group was significantly longer than that of the control group (P < 0.05). Hematoxylin-eosin staining results showed that in the experimental group, the number of hippocampal pyramidal cells decreased, the cell structure was disordered, and the nucleus was broken and dissolved. Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus, and the expressions of IP3R2, RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group (P < 0.05). Western blot analysis showed that the expressions of IP3R2, RYR2, and glial fibrillary acidic protein in the hippocampus of the experimental group were increased (P < 0.05). Ca2+ concentration in hippocampal astrocytes increased significantly in the experimental group (P < 0.05). To conclude, astrocytes may affect Ca2+ signals by mediating IP3R2 and RYR2 receptors, then impair the cognitive function of mice with carbon monoxide poisoning, and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

Key words: delayed encephalopathy after acute carbon monoxide poisoning, astrocyte, IP3R2 receptor, RYR2 receptor, calcium signaling, cognitive function

CLC Number:

Zhao Jili, Meng Tianyu, Yue Yarong, Zhang Xin, Du Wenqian, Zhang Xinyu, Xue Hui, Xiang Wenping. Expression of IP3R2 and RYR2 mediated Ca2+ signals in a mouse model of delayed encephalopathy after acute carbon monoxide poisoning [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(2): 254-261.

Figures/Tables 9

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