Reassessment subacute MPTP-treated mice model of Parkinson disease / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE ① To estimate the value of the subacute MPTP mouse model in aspects of behavioral performance, biochemical changes and pathological abnormalities. ② To find effective positive drugs. METHODS Male 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. RESULTS The 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. CONCLUSION The 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.