Parkinson＇s disease （PD） is disorder affecting more than a common neurodegenerative 1% people above 60 years of age worldwide, manifesting as the impaired motor function such as tremors, rigidity, akinesia/bradykin...Parkinson＇s disease （PD） is disorder affecting more than a common neurodegenerative 1% people above 60 years of age worldwide, manifesting as the impaired motor function such as tremors, rigidity, akinesia/bradykinesia and postural inefficiency with a reduced life expectancy （Dorsey et al., 2007）. PD is believed to be the end result of the progressive death of dopaminergic neurons in the substantia nigra pars compacta （SNc）.展开更多
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 C57 BL/6 mi...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 C57 BL/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 performance 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.展开更多
基金supported by funding from CSIR network project(BSC0115)
文摘Parkinson＇s disease （PD） is disorder affecting more than a common neurodegenerative 1% people above 60 years of age worldwide, manifesting as the impaired motor function such as tremors, rigidity, akinesia/bradykinesia and postural inefficiency with a reduced life expectancy （Dorsey et al., 2007）. PD is believed to be the end result of the progressive death of dopaminergic neurons in the substantia nigra pars compacta （SNc）.
基金supported by National Natural Science Foundation of China(81373997,U1402221,81573640 and 81603316)Beijing Natural Science Foundation(7161011)+3 种基金Beijing Key Laboratory of New 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)Scientific Research Foundation of the Higher Education Institutions of Hunan Province(15K091)
文摘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 C57 BL/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 performance 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.
