title: Participation of perforin in mediating dopaminergic neuron loss in MPTP-induced Parkinson's disease in mice.
abstract: Both resident innate and peripheral immune aberrations have been demonstrated to influence Parkinson's disease (PD) progression. However, it is still enigmatic how and which immune components are lethal to the dopaminergic neuron in PD. We now show that levels of perforin, a pore-forming protein expressed in cytotoxic immune cells, was significantly increased in the serum of wild-type mice 4 weeks after injection of MPTP, a toxin used to induce PD-like symptoms. We demonstrate that perforin-deficiency attenuated the acute striatal dopamine reduction by 33%, ablated microglia activation 3 days post MPTP-injection; and retarded dopaminergic neuron death 4 weeks post MPTP-injection. Our study suggests that perforin plays a role in dopaminergic neuron loss in PD.
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, PR China; Department of Neuroscience, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Su-Ping
authors.initials: SP
authors.lastname: Peng
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Sjef
authors.initials: S
authors.lastname: Copray
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, PR China; W. M. Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08845, USA. Electronic address: schachner@stu.edu.cn.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, PR China; Center for Neuroscience, Jiangnan University Medical School, Wuxi, Jiangsu 214122, PR China. Electronic address: shenyanqin@jiangnan.edu.cn.
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Shen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology*; D054353:Perforin / Q000378:metabolism*
chemical_list: D054353:Perforin
keywords: Dopaminergic neuron; Microglia; Neuroinflammation; Parkinson's disease; Perforin