Neuroprotection effects of retained acupuncture in neurotoxin-induced Parkinson’s disease mice

Abstract

The aim of this study was to investigate the role of retained acupuncture (RA) in neurotoxin-induced Parkinson’s disease (PD) mice. Male C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce the PD model. The mice were divided into four groups, namely, (1) normal; (2) MPTP + retained acupuncture (RA); (3) MPTP + electroacupuncture (EA); (4) MPTP + sham acupuncture (SA). After mice being manipulated with/without acupuncture at acupoints (Daling, PC 7), groups 2–4 were injected with MPTP (15 mg/kg/d). The mice were evaluated for behavioral changes, in terms of time of landing, after acupuncture treatment. The animals were sacrificed and their brains assayed for dopamine and its metabolites and tyrosine hydroxylase (TH) expression by using HPLC and immunohistochemistry/Western blotting, respectively. [¹²³I] IBZM-SPECT imaging between SA and RA groups were compared. The results showed that the time of landing of the three groups with treatment was significant longer than group 1 (normal) (4.33 ± 0.15 s). Nonetheless, group 2 (RA) (7.13 ± 0.20 s) had a shorter time of landing than group 4 (SA) (7.89 ± 0.46 s). The number of TH (+) neurons and the expression of TH proteins were significantly higher in the RA group than in the SA/EA groups. RA also increased the uptake of [¹²³I] IBZM into the triatum compared to the SA group. We conclude that RA possibly attenuates neuronal damage in MPTP-induced PD mice, which suggests RA may be useful as a complementary strategy when treating human PD.

Introduction

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and affects about 1–2% of individuals over the age of 60 (Gasser, 2009). In Taiwan, it is estimated that the crude prevalence rate of idiopathic PD in persons aged 40 years and over is 706 per 100,000 individuals (Chen et al., 2009). PD is characterized by symptoms including rest tremors, postural instability, gait abnormality, bradykinesia and rigidity. The major pathological change of Parkinson’s disease is a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), the loss of striatal dopaminergic fibers, a dramatic reduction in the striatal dopamine levels and the presence of neuronal proteinaceous aggregates called Lewy bodies (LBs) (Schober, 2004).

The exact etiology of PD, though extensively studied, remains unknown. A number of factors including oxidative stress, mitochondrial dysfunction, inflammation and apoptosis have been implicated in the pathogenesis of PD (Mounsey and Teismann, 2010). Accumulating evidence suggests that exposure to environmental toxins and genetic aberrance lead to dopaminergic neuronal loss and clinical Parkinsonism (Fahn, 2010, Liang et al., 2003, Przedborski et al., 2001). Current clinical therapy for PD is largely based on a dopamine replacement strategy, primarily by administration of the dopamine precursor levodopa; however, this is often associated with the development of levodopa-related motor complications (Stowe et al., 2010, Tomlinson et al., 2010). Many different treatment strategies such as genetic and implant therapies have been evaluated for neuroprotection and neuroprevention in the laboratory and in a clinical context (Fu et al., 2006, Poewe, 2009), but the outcome is far from satisfactory.

Since the 1990s the use of complementary and alternative medicine (CAM) worldwide has increased (Eisenberg et al., 1993). Therapies such as dietary supplements, vitamin therapy, exercise, physical therapy and massage therapy are reported to influence the symptoms of PD and/or the effectiveness of dopaminergic therapy (Zesiewicz and Evatt, 2009). Acupuncture therapy has been reported to show possible therapeutic effectiveness for PD in clinical trials, as manifested by an ameliorating of the clinical motor symptoms (Shulman et al., 2002) and an improvement in the quality of daily living (Zhuang and Wang, 2000); in addition acupuncture has no known interactions with other medication (Eng et al., 2006).

Previously, using functional magnetic resonance imaging (fMRI) and single photon emission computed tomography (SPECT), acupuncture analgesia has been shown to be a consequence of central modulation of the descending inhibitory pathway associated with pain sensation (Hsieh et al., 2001, Li et al., 2010, Wu et al., 2002). In human studies, activation of the hypothalamus has been identified as a cardinal finding of De-qi (Hsieh et al., 2001). Moreover, a recent fMRI study has suggested there is a cerebrocerebellar interaction during peripheral stimulation (Shih et al., 2009) and activation of the cerebellum can be visualized as occurring simultaneously with acupuncture treatment (Hsieh et al., 2001). This is indicative of an effect on the activation of extra-pyramidal system, an important area where the pathogenesis of PD occurs. Accordingly, it was our aim to investigate the effect of acupuncture on neurotoxin-induced PD mice.