Acupuncture inhibits autophagy and promotes synaptic repair by activating the PI3K/Akt/mTOR pathway in a rat model of depression in Parkinson’s disease

Abstract

Background:

Acupuncture may alleviate both the motor and depressive symptoms of Parkinson’s disease (PD); however, the underlying mechanism has not yet been elucidated. In this study, on the basis of previous findings that acupuncture improves depressive behaviors in a rat model of depression in Parkinson’s disease (DPD), we investigated whether manual acupuncture (MA) has a modulatory effect on the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, autophagy and prefrontal cortical synaptic repair proteins in a rat model of DPD.

Methods:

We screened 6-hydroxydopamine (6-OHDA)-induced DPD model rats and divided them into four groups: DPD group, DPD + MA group, DPD + PI3K group and DPD + MA + PI3K group. The latter two groups were injected with the PI3K inhibitor LY294002. A sham group injected with normal saline was also included. Twenty-eight days after the end of treatment, the expression of phosphorylated (p)-PI3K, p-Akt, p-mTOR, p-p70S6K (70 kDa ribosomal protein S6 kinase), p-4E-BP-1 (4E binding protein 1), p62, Beclin-1, Synapsin I and postsynaptic density protein (PSD)95 in the prefrontal cortex was determined by Western blotting. We used transmission electron microscopy (TEM) to study neuronal damage and evaluate the effect of MA on neurons and autophagy in the prefrontal cortex of DPD model rats.

Results:

MA upregulated the expression of p-PI3K, p-Akt, p-mTOR, p-p70S6K, p-4E-BP-1, p62, Synapsin I and PSD95, and decreased expression levels of Beclin-1, in the prefrontal cortex of DPD model rats. Acupuncture attenuated neuronal damage and reduced the number of autophagosomes in the prefrontal cortex of DPD model rats.

Conclusion:

Acupuncture may serve as a treatment for DPD by activating the PI3K/Akt/mTOR pathway to inhibit the process of autophagy and repair damaged synapses.