[Effects of electroacupuncture on cognitive impairment and mitophagy mediated by KIF5A/Miro1 pathway in Parkinson's disease mice].

OBJECTIVE

To explore the improvement effect of electroacupuncture (EA) based on acupuncture (acupuncture for regaining consciousness and opening orifices) on cognitive impairment in mice with Parkinson's disease (PD), and to explore its regulatory mechanisms on the kinesin family member 5A (KIF5A)/mitochondrial Rho GTPase 1 (Miro1) pathway and mitophagy in prefrontal cortical neurons.

METHODS

A total of 70 male C57BL/6J mice of clean grade were randomly divided into a normal group (12 mice), a sham operation group (12 mice), and a model pre-screening group (46 mice). Unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle was adopted to establish the PD model in the model pre-screening group. Twenty-four mice after successful modeling were randomly selected and divided into a model group and an EA group, 12 mice in each one. In the EA group, acupuncture was applied at "Shuigou" (GV26) and bilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6), ipsilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6) were connected to EA respectively, with disperse-dense wave, 5 Hz/20 Hz in frequency, 0.5 mA in current intensity, 20 min a time, 6 times a week for 30 days. Cognitive function was assessed by Y-maze and Morris water maze tests; morphology of prefrontal cortex was observed by H.E. staining; reactive oxygen species (ROS) level in prefrontal cortex was detected by fluorescence probe method; mitochondrial morphology and autophagosome ultrastructure were observed by transmission electron microscopy; the mRNA expression of tyrosine hydroxylase (TH) was detected by quantitative real-time PCR; the protein expression of TH, KIF5A, Miro1, p62, Parkin and PTEN induced kinase 1 (PINK1) was detected by Western blot.

RESULTS

Compared with the sham operation group, both the model group and the EA group exhibited increased rotation number of per minute (<0.001). Compared with the sham operation group, in the model group, the novel arm exploration time of Y-maze test was shortened (<0.001), the escape latency of Morris water maze test was prolonged (<0.05) and the platform crossing number of Morris water maze test was reduced (<0.01); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was increased (<0.001), and mitochondrial autophagosomes could be observed; in the prefrontal cortex, the relative expression of ROS was increased (<0.001), the protein and mRNA expression of TH was decreased (<0.001), the protein expression of Miro1, PINK1, Parkin was increased (<0.001, <0.01), the protein expression of KIF5A and p62 was decreased (<0.001). Compared with the model group, in the EA group, the novel arm exploration time of Y-maze test was prolonged (<0.01), the escape latency of Morris water maze test was shortened (<0.05) and the platform crossing number of Morris water maze test was increased (<0.05); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was decreased (<0.001), and the number of mitochondrial autophagosomes reduced and the mitochondrial morphology was improved; in the prefrontal cortex, the relative expression of ROS was decreased (<0.01), the protein and mRNA expression of TH was increased (<0.001, <0.01), the protein expression of Miro1, PINK1, Parkin was decreased (<0.001, <0.01, <0.05), the protein expression of KIF5A and p62 was increased (<0.01, <0.05).

CONCLUSION

electroacupuncture effectively alleviates cognitive impairment and damage of neuronal function in PD mice, its mechanism may be related to the regulation of KIF5A/Miro1 pathway, hence reducing the mitophagy in prefrontal cortical neurons.