Lu WEN,Yu-he YUAN,Nai-hong CHEN,2

(1.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of MateriaMedica&Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;2.College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China)

T3-15

Reassessment subacute MPTP-treated mice model of Parkinson disease

Lu WEN1,Yu-he YUAN1,Nai-hong CHEN1,2

(1.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of MateriaMedica&Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;2.College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China)

OBJECTIVE①To estimate the value of the subacute MPTP mouse model in aspects of behavioral performance,biochemical changes and pathological abnormalities.②To find effective positive drugs.METHODSMale C57BL/6 mice were injected with MPTP(30 mg·kg-1·d-1,ip)for 5 consecutive days.Three days before MPTP injection,the mice were orally administered selegiline(3 mg·kg-1·d-1),pramipexole(3 mg·kg-1·d-1),or medopar(100 mg·kg-1·d-1)for 18 d.Behavioral perfor?mance was assessed in the open field test,pole test and rotarod test.Neurotransmitters in the striatum were detected using HPLC.Protein levels were measured by Western blot.Pathological characteristics were examined by immunohistochemistry.Ultrastructure changes were observed by electron microscopy.RESULTSThe subacute MPTP treatment did not induce evident motor defects despite severe injuries in the dopaminergic system.Additionally,MPTP significantly increased the α-synuclein levels and the number of astrocytes in the striatum,and destroyed the blood-brain barrier(BBB)in the substantianigra pars compacta.Both selegiline and pramipexole were able to protect the mice against MPTP injuries.CONCLUSIONThe subacute MPTP mouse model does not show visible motor defects;it is not enough to evaluate the validity of a candidate just based on behavioral examination,much attention should also be paid to the alterations in neurotransmitters,astrocytes,α-synuclein and the BBB.In addition,selegiline or pramipexole is a better choice than medopar as an effective positive control for the subacute MPTP model.

subacute MPTP model;Parkinson disease;selegiline;pramipexole;α-synuclein

The project supported by National Natural Science Foundation of China(81373997,U1402221,81573640 and 81603316);Beijing Natural Science Foundation(7161011);Beijing Key Laboratory ofNew Drug Mechanisms and Pharmacological Evaluation Study(BZ0150);CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004);Key Research and Development Project of Hunan Province(2015SK2029-1);and Scientific Research Foundation of the Higher Education Institutions of Hunan Province(15K091)

Yu-he YUAN,Tel:(010)63165182,E-mail:yuanyuhe@imm.ac.cn;Nai-hong CHEN,Tel:(0 10)63165177,E-mail:chennh@imm.ac.cn