[40 Hz flicker light stimulation suppresses STING signaling to improve cognitive dysfunction in mice with Parkinson...

To explore the effects of 40 Hz flicker light stimulation on cognitive dysfunction in mice with subacute Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the underlying mechanisms.

Forty 8-week-old male C57BL/6 mice were randomly allocated to a control group and 4 MPTP-induced PD model groups receiving blank treatment, 40 Hz flicker light stimulation, or stereotactic intraventricular injection of a control AAV (sh-NC) or an AVV carrying sh-STING. After the treatments, the mice were examined for changes in motor functions and cognitive behaviors. Immunofluorescence staining, Nissl staining, ELISA, Western blotting and RT-qPCR were used to detect hippocampal co-localization of S100A10 and C3 with GFAP, Nissl neuron count, serum interleukins, and nigral and hippocampal expressions of α-syn, TH, synaptic, astrocytic, inflammatory, SOCS3, JAK2-STAT3, and the STING pathway at the mRNA and protein levels.

The PD mouse models exhibited impaired motor and cognitive functions with lowered TH and elevated α‑syn expressions. 40 Hz light flicker stimulation improved cognitive function of the PD mice, significantly increased the number of hippocampal neurons and S100A10 expression, and reduced the expressions of p-STING/STING, C3, GFAP, IL-6, and TNF‑α. Compared with the PD mice with sh-NC injection, the mice receiving sh-STING AVV injection showed significantly improved cognitive function with lowered hippocampal expression level of C3 and increased expression of S100A10 without significant changes in the expression levels of SOCS3 and JAK2-STAT3.

40 Hz flicker light stimulation mitigates impairment of cognitive function in mice with MPTP-induced PD by inhibiting STING overactivation to promote A2 astrocyte polarization and enhance hippocampal synaptic plasticity.