absence of ret signaling in mice causes progressive and late degeneration of the nigrostriatal system老鼠缺乏ret信号导致进步和晚期黑系统的退化.pdfVIP

PLoS BIOLOGY Absence of Ret Signaling in Mice Causes Progressive and Late Degeneration of the Nigrostriatal System 1* 1 2 3,4 5 6 2 Edgar R. Kramer , Liviu Aron , Geert M. J. Ramakers , Sabine Seitz , Xiaoxi Zhuang , Klaus Beyer , Marten P. Smidt , ¨ 1* Rudiger Klein 1 Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, Martinsried, Germany, 2 Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands, 3 Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany, 4 Institute for Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany, 5 Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois, United States of America, 6 Department of Metabolic Biochemistry, Adolf Butenandt Institute, Munich, Germany Support of ageing neurons by endogenous neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. GDNF has been tested in clinical trials for the treatment of Parkinson disease (PD), a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA neurons in PD animal models. The physiological roles of GDNF and BDNF signaling in the adult nigrostriatal DA system are unknown. We generated mice with regionally selective ablations of the genes encoding the receptors for GDNF (Ret) and BDNF (TrkB). We