| Parkinson's disease (PD) is one of the major neurodegenerative disorders, characterized by a progressive and selective degeneration and necrosis of dopaminergic neurons in substantia nigra (SN), as well as the decrease of dopamine (DA) content in striatum, which results in movement dysfunction. Many studies reported that the death of dopaminergic neurons in parkinsonism may be due to many causes, for instance, oxidative stress, apoptosis and mitochondria dysfunction. Therefore, the drugs used in Parkison's disease may be neuroprotective and anti-apoptosis agents that protect the brain from the damaging effects of the disease. So, Chinese traditional medicine become a effective therapeutic strategies aiming at halt the natural progression of PD, lessening the side effects and control some symptoms.Ginseng (Panax ginseng) has been used as a tonic in Chinese traditional medicine for two thousand years. It is very useful to restore the deteriorated functions of aged persons and animals. Ginsenoside Re is one of the important active principles of ginseng and shares many pharmacological effects of this plant. Our previous work found that Re had the effect of anti-oxidation and clearing out of the oxygen-derived free ridicals, with others Ginsenoside Rbl, Rb3, Rgl et al. We had also reported Repossessed the effect of anti-oxidative stress and it related to regulating the synthesization and metabilizability of monamine transmitter. Thus, this indicates that Re possibly has the therapeutic effect on PD.In the present study, the protective effect of Re on dopaminergic neurons in substantia nigra pars compacta (SNc) was investigated by the PD model mice treated with l-methy-4-phenyl-l, 2, 3, 6- tetrahydropyridine (MPTP). Behavior, high-performance liquid chromatographgy with electrochemical detector, immunohischemistry, in situ hybridization, TDT-mediated dUTP nick-end labeling (TUNEL) staining, western blots analysis and transmission electron microscope (TEM) technique were used to observe respectively the damage of substantia nigral neurons. Meanwhile, the cytomolecular possible mechanism of action on therapeutic was also studies. The results are as followings:1. The protective effect of Re on morphology and function of dopaminergic neurons in substantia nigra compacta (SNc) in MPTP-treated mice.In the pole test, traction test and the swimming test, the model group mice demonstrated dyskinesia, scores obtained from the three behavioral tests were decreased significantly compared with control group ; while the scores in Pretreatment groups (26, 13 mg kg-1) showed a marked increase to some degree. These results suggested that Re could improve the dyskinesia of PD mice.The contents of DA and HVA were detected by HPLC-ECD to be decreased approximately by 84% and 65%, respectively. The ratio of HVA/DA increased in model group compared with control group (p<0.01); In pretreatment groups, the contents of DA and HVA were recovered significantly and the ratio of HVA/DA decreased. The IHC of TH showed that, there was seldom TH positive neurons in SNc (p<0.01) in model group; while there were much more TH positive neurons presented in the pretreatment groups than that in model group. Thus, many results proved succeed of this PD mouse model and the protective effect of Re on dopaminergic neurons in SN.GFAP positive astrocytes were obviously increased at SN (p<0.01) by IHC in model group; Compared with control group, there was no significantly increase ofGFAP positive astrocytes in pretreatment groups (p<0.01). The data indicated Re could prevent the proliferation of astrocyte in SNThe results of GABA IHC showed that GABA positive neurons markedly decreased in model group SN pars reticular and striaral area in PD model mice as compared with control group (P<0.05). However, in pretreatment group, there were no significantly decreases of GABA positive in above areas. The results of experiment showed Re could increase the expression of GAB Aergic neuron in CPu and SNr area of basal ganglia and regulate... |
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