Electroacupuncture regulates glucose metabolism by inhibiting SGLT1 levels, inhibiting microglial polarization, and alleviating Parkinson's disease.

BACKGROUND

Parkinson's disease (PD) is a common central neurodegenerative disease in middle-aged and elderly people. The progressive degeneration and death of dopaminergic neurons leads to insufficient dopamine (DA) neurotransmitters. Acupuncture and moxibustion can alleviate the aging of neurons. Therefore, studying the neuroprotective effects of electroacupuncture (EA) in PD mice is particularly important.

METHODS

Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was used to establish a PD mouse model, and lipopolysaccharide (LPS) was used to induce microglia polarization. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Nissl staining and immunohistochemistry were used to detect neuronal apoptosis and injury, α-syn expression and microglial accumulation in PD mice. In addition, the levels of inflammatory factors were determined using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the Ca content. The fluorescein isothiocyanate (FITC) labeling method was used to assess glucose uptake. A reagent kit was used to detect glucose and lactate levels.

RESULTS

MPTP induced the selective loss of DA neurons in the SN of mice, altered Ca homeostasis, and induced an inflammatory response. In addition, maintaining Ca homeostasis depends on the activity of transient receptor potential channel 1 (TRPC1). EA therapy promotes TRPC1 expression, which has a negative regulatory effect on sodium-glucose cotransporter 1 (SGLT1). Under the action of EA, TRPC1 protein expression increased, Ca concentrations increased, and the effect of SGLT1 was inhibited, thereby facilitating glucose metabolism, blocking the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, restraining M1 polarization of microglia, and alleviating the PD process.

CONCLUSION

EA promotes TRPC1/Ca pathway activation, inhibits SGLT1-mediated regulation of glucose metabolism and PI3K/AKT pathway activation, inhibits microglial M1 polarization, and alleviates PD.