Dopaminergic Neuron Damage induced by Constant Intragastric Administration of Low-dose Rotenone
HUANG Meng-yang;JIANG Hong;HU Qi;KANG Hui-cong;XU Feng;LIU Xiao-yan;ZHANG Cun-tai;ZHU Sui-qiang;Department of Geriatrics,TongJi Hospital,TongJi Medical College,Huazhong University of Science and Technology;
Objective:To explore the mechanism of dopaminergic neuron damage induced by constant intragastric administration of low-dose rotenone. Methods: Fifty aged male mice were randomly divided into Parkinson disease(PD) model group and control group. The mice in PD model group were administrated 0.01 mL/g rotenone by gavage while the mice in control group were administrated 0.01 mL/g chloroform. Before treatment and 6 weeks, as well as 12 weeks after treatment, alpha-synuclein(α-Syn), Thioflavin S(ThS) and tyrosine hydroxylase(TH) were detected in neurons from gastrointestinal tract, thoracic spinal cord and midbrain of both the control and treated animals. Simultaneously, ultrastructural changes were observed by electron microscopy 12 weeks after treatment. Results: Six weeks after treatment, immunofluorescence demonstrated that α-Syn and ThS were increased in intestinal intramural plexus and thoracic spinal cord in the PD model group compared to the controls while the expression of α-Syn and number of TH positive neurons in midbrain did not show any significant changes(P0.05). However, 12 weeks after treatment, immunofluorescence showed that there was an increase in α-Syn and an significant decrease in TH positive neurons in the midbrain(P=0.011) in the model group compared with those in the controls. Moreover, electron microscopy showed a lot of abnormalities in the PD model group, such as the swollenness of cell membrane, mitochondria and endoplasmic reticulum, alterations of nuclei, and necrosis of neurons in the substantia nigra, in a sharp contrast to the normality in the.control group. Conclusion: Dopaminergic neuron damage was observed in mouse brain after constant intragastric administration of low-dose rotenone, probably mediated by the spread of synuclein aggregates formed in gastrointestinal plexues into brain by prion-like transmission.