Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN). Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931) probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes) affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by major behavioral symptoms, which include tremor, akinesia, bradykinesia, and stiffness (Jankovic, 2008)
Because tyrosine hydroxylase (TH) expression is significantly attenuated in the brains of PD patients (Pardridge, 2005) and in Parkinsonism animal models (Park et al, 2003; Kang et al, 2007; Choi et al, 2009), we evaluated TH levels to confirm the establishment of a chronic MPTP-induced Parkinsonism mouse model and the mediating effects of acupuncture at GB34 and LR4
Immunohistochemical analyses using Western blots confirmed that the decrease in TH levels in the striatal and SN pars compacta (SNpc) regions induced by MPTP intoxication was significantly inhibited by acupuncture at acupoints (MPTP-A) but not at non-acupoints (MPTP-NA; Figure 2)
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by major behavioral symptoms, which include tremor, akinesia, bradykinesia, and stiffness (Jankovic, 2008). Using a 6-hydroxydopamine (6-OHDA)-induced Parkinsonism model, a previous study found that acupuncture stimulation at acupoints GB34 and LR3 results in the enhanced survival of dopaminergic neurons in the SN and a ~87.7% improvement in motor dysfunction (Park et al, 2003). Similar finding were found following the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where the acupuncture-induced enhancement of synaptic dopamine availability may play a critical role in the observed motor function improvement (Kim et al, 2011). Acupuncture stimulation at the same acupoints attenuates the decrease in tyrosine hydroxylase (TH) immunoreactivity (IR) and generates neuroprotective effects in the SN in an MPTP-induced mouse model of Parkinsonism (Kang et al, 2007). The mechanisms underlying the neuroprotective effects of acupuncture on the SN are thought to be in part related to decreased microglial activation and reduced inflammatory responses (Kang et al., 2007); these, in turn, inhibit ferric iron and ferritin heavy chain deposition (Choi et al, 2009)
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