Acupuncture Inhibits the Increase in Alpha-Synuclein by Modulating SGK1 in an MPTP Induced Parkinsonism Mouse Model.

Abstract

Parkinson's disease (PD), a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein ( -syn) along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in -syn expression that is related with dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase. Moreover, acupuncture stimulation attenuated the increase in -syn. We identified that serum- and glucocorticoid-dependent kinase 1 (SGK1) is evidently downregulated in chronic MPTP-intoxication and acupuncture stimulation maintained SGK1 expression at levels similar to the control group. For an examination of the expression correlation between SGK1 and -syn, SH-SY5Y cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of -syn were observed. Our findings indicate that the acupuncture-mediated inhibition in the -syn increase induced by MPTP may be responsible for modulating SGK1 expression.