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Role of IGF1/IGFR signaling pathway in neuroprotective effect of Shengmai Dihuang Decoction on CIH-induced cognitive impairment

Year: 2024

Type: article

Abstract: As the most important pathophysiological process of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) could cause cognitive impairment. Our previous study showed that Shengmai Dihuang Decoction (SDD) improved CIH-induced cognitive impairment. However, the precise underlying mechanism remains unclear. This study aims to investigate the role of the insulin-like growth factor 1 (IGF1)/insulin-like growth factor 1 receptor (IGFR) signaling pathway in improving CIH-induced neuronal injury by SDD treatment. In this study, HT22 cells were cultured under CIH conditions (O 2 : 21–0.1 %, 6 cycles/h). Cell ability was assessed by CCK-8 assay, and Mitochondrial damage was detected by transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), ATP, and mitochondrial complex I activity assay. Mitochondrial oxidative stress was detected by MitoSOX superoxide indicator. IGF1/IGFR signaling pathways were detected by Elisa, immunofluorescence staining, and Western blot. In addition, C57BL/6 mice were exposed to CIH for 35 days (O 2 : 21-5%, 8 h/d), and cognitive impairment was assessed by Morris water maze. Results showed that cell activity was decreased during CIH exposure, followed by mitochondrial damage and decreased IGF1/IGFR expressions. Exogenous IGF1 treatment increased cell activity and improved mitochondrial dysfunction. SDD treatment increased IGF1/IGFR expressions, activated the RAS/RAF/MAPK and PI3K/AKT signaling pathways, increased ERK/CREB/BDNF and postsynaptic density protein 95 (PSD-95) expressions, and improved mitochondrial damage and cell activity. IGF1 siRNA or AG1024 (IGFR antagonist) reversed the protective effects of SDD under CIH condition. Results suggest that SDD alleviates CIH-induced neuronal injury, mainly by improving mitochondrial damage via activation of IGF1/IGFR signaling pathway.

Source: Journal of Traditional and Complementary Medicine

DOI: 10.1016/j.jtcme.2024.11.014