Acupuncture regulates α-synuclein expression via serping1 in an MPTP-induced mouse model of Parkinsonism.

Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by a substantial loss of dopaminergic cells in the substantia nigra (SN) and the formation of intracellular Lewy bodies, which are mainly composed of α-synuclein (α-syn). Acupuncture has been used to improve the symptoms of PD in humans and exhibits a neuroprotective effect against Parkinsonism in animal models. We further investigated the neuroprotective effect of acupuncture via its effect on α-syn levels, dopaminergic cell death and serping1 expression in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of chronic PD.

Methods: Mice were divided into a control group receiving phosphate-buffered saline (CTL) and three model groups receiving MPTP that either remained untreated (MPTP) received verum acupuncture at GB34 and LR3 (MPTP_A) or received control acupuncture at sites not corresponding to any traditional acupuncture point location (MPTP_NA). The signal intensity of serping1 gene expression was assessed using microarray, and α-syn level and dopaminergic cell death were measured by Western blotting, immunohistochemistry and immunofluorescence. To further investigate the relationship between expression of serping1 and α-syn, a cell culture experiment was carried out in a 1-methyl-4-phenylpyridinium (MPP+) treated neuroblastoma cell line (SH-SY5Y) with and without serping1 knockdown using short interfering (si)RNA.

Results: Acupuncture at GB34 and LR3 attenuated the MPTP-induced decrease in tyrosine hydroxylase (TH) levels and increase in α-syn levels in the SN. Furthermore, verum acupuncture prevented the increase in serping1 level induced by MPTP. In SH-SY5Y cells, MPP+ treatment increased α-syn and decreased both TH expression and cell viability; however, these effects were mitigated by serping1 knockdown.

Conclusions: Our results suggest that an MPTP-induced reduction in serping1 level leads to decreased TH and increased α-syn expression, and that these effects can be attenuated/blocked by acupuncture at GB34 and LR3. Our findings provide new evidence for the neuroprotective effects of acupuncture on dopaminergic cells, which may be mediated by control of serping1 expression.