Neuroprotective Changes of Striatal Degeneration-Related Gene Expression by Acupuncture in an MPTP Mouse Model of Parkinsonism: Microarray Analysis
- 431 Downloads
Acupuncture at acupoints GB34 and LR3 has been reported to inhibit nigrostriatal degeneration in Parkinsonism models, yet the genes related to this preventive effect of acupuncture on the nigrostriatal dopaminergic system remain elusive. This study investigated gene expression profile changes in the striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism models after acupuncture at the acupoints GB34 and LR3 using a whole transcript genechip microarray (Affymetrix genechip mouse gene 1.0 ST array). It was confirmed that acupuncture at these acupoints could inhibit the decrease of tyrosine hydroxylase and dopamine transporter in the nigrostriatal region of the MPTP model while acupuncture at the non-acupoints could not counteract this decrease. Genechip gene array analysis (fold change cutoff 1.3 and P < 0.05) showed that 12 of the 69 probes up-regulated in MPTP when compared to the control were down-regulated by acupuncture at the acupoints. Of these 12 probes, 11 probes (nine annotated genes) were exclusively down-regulated by acupuncture only at the acupoints; the Gfral gene was excluded because it was commonly down-regulated by acupuncture at both the acupoints and the non-acupoints. In addition, 28 of the 189 probes down-regulated in MPTP when compared to the control were up-regulated by acupuncture at the acupoints. Of these 28 probes, 19 probes (seven annotated genes) were exclusively up-regulated by acupuncture only at the acupoints while nine probes were commonly up-regulated by acupuncture at both the acupoints and the non-acupoints. The regulation patterns of representative genes in real-time RT-PCR correlated with those of the genes in the microarray. These results suggest that the 30 probes (16 annotated genes), which are affected by MPTP and acupuncture only at the acupoints, are responsible for exerting in the striatal regions the inhibitory effect of acupuncture at the acupoints on MPTP-induced striatal degeneration.
KeywordsParkinson’s disease Gene array Differentially expressed genes Striatum Neurodegeneration
This work was supported by the Mid-career Researcher Program through an NRF grant funded by the MEST, Republic of Korea (No. 2010-0000385).
- Bouzas-Rodriguez J, Cabrera JR, Delloye-Bourgeois C, Ichim G, Delcros JG, Raquin MA, Rousseau R, Combaret V, Bénard J, Tauszig-Delamasure S, Mehlen P (2010) Neurotrophin-3 production promotes human neuroblastoma cell survival by inhibiting TrkC-induced apoptosis. J Clin Invest 120:850–858CrossRefPubMedGoogle Scholar
- Fornai F, Schlüter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G, Pellegrini A, Nicoletti F, Ruggieri S, Paparelli A, Südhof TC (2005) Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci USA 102:3413–3418CrossRefPubMedGoogle Scholar
- Hong MS, Park HK, Yang JS, Park HJ, Kim ST, Kim SN, Park JY, Song JY, Park HK, Jo DJ, Park SW, HwanYun D, Ban JY, Chung JH (2010) Gene expression profile of acupuncture treatment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease model. Neurol Res 32:74–78CrossRefPubMedGoogle Scholar
- Mandel S, Grunblatt E, Riederer P, Amariglio N, Jacob-Hirsch J, Rechavi G, Youdim MB (2005) Gene expression profiling of sporadic Parkinson’s disease substantia nigra pars compacta reveals impairment of ubiquitin-proteasome subunits, SKP1A, aldehyde dehydrogenase, and chaperone HSC-70. Ann NY Acad Sci 1053:356–375CrossRefPubMedGoogle Scholar
- Miwa T, Watanabe A, Mitsumoto Y, Furukawa M, Fukushima N, Moriizumi T (2004) Olfactory impairment and Parkinson’s disease-like symptoms observed in the common marmoset following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Acta Otolaryngol Suppl 553:80–84CrossRefPubMedGoogle Scholar
- Park HJ, Lim S, Joo WS, Yin CS, Lee HS, Lee HJ, Seo JC, Leem K, Son YS, Kim YJ, Kim CJ, Kim YS, Chung JH (2003) Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson’s disease model. Exp Neurol 180:93–98CrossRefPubMedGoogle Scholar
- Pirkevi C, Lesage S, Brice A, Başak AN (2009) From genes to proteins in mendelian Parkinson’s disease: an overview. Anat Rec (Hoboken) 292:1893–1901Google Scholar
- Russo MA, Giustizieri ML, Favale A, Fantini MC, Campagnolo L, Konda D, Germano F, Farini D, Manna C, Siracusa G (1999) Spatiotemporal patterns of expression of neurotrophins and neurotrophin receptors in mice suggest functional roles in testicular and epididymal morphogenesis. Biol Reprod 61:1123–1132CrossRefPubMedGoogle Scholar