Acupuncture alleviates neuro-inflammatory injury in rats with cognitive impairment induced by Parkinson's disease based on cGAS-STING signaling pathway.

Objectives: To observe the effect of acupuncture on neuro-inflammation in rats with cognitive impairment induced by Parkinson's disease (PD) based on the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway.

Methods: SD rats were randomly grouped into sham operation, model, acupuncture, acupuncture+empty and acupuncture+cGAS over-expression groups, with 12 rats in each group. The PD model was established by injecting 6-hydroxydopamine (6-OHDA, 8 μg/rat) into the substantia nigra pars compacta of the left midbrain (AP:-5.2 mm, ML:2.1 mm, DV:-7.8 mm). Acupuncture was conducted for rats in the acupuncture, acupuncture+empty and acupuncture+cGAS over-expression groups, for 20 min, once daily; empty plasmid or cGAS over-expression plasmid was injected into the substantia nigra pars compacta of the left midbrain for rats of the acupuncture+empty or acupuncture+cGAS over-expression groups respectively, twice a week. The same volume of 0.9% sodium chloride solution was injected for rats in the sham operation, model and acupuncture groups, twice a week. All above interventions were performed for 2 weeks. The rotation behavior of rats was detected by apomorphine-induced rotation experiment. The cognitive function was detected by Morris water maze test and dark avoidance test. Nissl staining was used to detect the pathological morphology and the number of hippocampal neurons. TUNEL staining was used to detect the apoptosis rate of hippocampal neurons. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and midbrain tissue were detected by ELISA. Western blot was used to detect the expression levels of cGAS and STING proteins in midbrain tissue.

Results: Compared with the sham operation group, the rotation speed, the escape latency in the Morris water maze test and the number of errors in the dark avoidance test, the apoptosis rate of hippocampal neurons, the contents of TNF-α and IL-1β in serum and midbrain tissue, and the expression levels of cGAS and STING protein in midbrain tissue were increased (<0.05), while the times of crossing the original platform in the Morris water maze test, the latency in the dark avoidance test and the number of hippocampal neurons were decreased (<0.05) in the model group, the hippocampal neurons were disordered. All the indexes mentioned above were reserved in the acupuncture and acupuncture+empty groups (<0.05), and there was no significant difference of all indexes between these two groups. After injection of cGAS over-expression plasmid, compared with acupuncture group, the rotation speed, the escape latency in the Morris water maze test and the number of errors in the dark avoidance test, the apoptosis rate of hippocampal neurons, the contents of TNF-α and IL-1β in serum and midbrain tissue, and the expression levels of cGAS and STING protein in midbrain tissue were increased (<0.05), while the times of crossing the original platform in the Morris water maze test, the latency in the dark avoidance test and the number of hippocampal neurons were decreased (<0.05), the hippocampal neurons were disordered.

Conclusions: Acupuncture can improve the cognitive impairment of PD rats, which may be related to its functions in blocking the cGAS-STING signal transduction, inhibiting the neuroinflammatory response, and reducing the damage and apoptosis of hippocampal neurons.