| Parkinson's disease (PD) is a neurodegenerative progressive disorder prevalent in the population above 45 years of age, which is characterized by the progressive and massive degeneration of mid-brain dopaminergic neurons, primarily from the substantia nigra pars compacta. The clinical symptoms are caused by the loss of dopaminergic neurons that exceed 50% of all and the consequent dysfunction of the nigrostriatal pathway. The disease is detected as a mild resting tremor of one or more limbs, muscular rigidity, postural abnormalities and bradykinesia-akinesia. The mechanism and pathogeny by which dopaminergic neurons degenerate in PD is still unknown, several risk factors have been associated with the disease, including age, genetic and environmental factors.Exposure to agricultural chemicals has long been suggested as a risk factor for PD. The identification of 1-methyl-4-phenyl-1,2,3-tetrahydropyridine (MPTP), a by-product of illicit heroin synthesis, as the culprit that induced Parkinson syndromes in humans has significantly intensified the search for environmental factors as potential causes of PD. The structural similarity between 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of MPTP, and a common herbicide, paraquat (PQ), prompted speculation that PQ might be a dopaminergic neurotoxicant. Case reports initially associated exposure to maneb (MB), a widely used fungicide, with the development of parkinsonism in humans. Furthermore, besides being toxic to dopaminergic neurons by itself, repeated systemic administration of MB and PQ to mice induced a synergistic reduction in ST dopamine content, degeneration of SN dopaminergic neurons, and development of motor behavioral abnormalities.Current treatment can not prevent nigral neurons from progressive death and pathological progress of PD. It is necessary, thus, to investigate novel methods of Traditional Chinese Medicine on protecting nigral dopamine neurons and improving the treatment of PD. 2, 3, 5, 4-Tetrahydroxystilbene -2-O-β-D-glucoside (TSG) is the main ingredient found in Polygonum multiflorum. Recently, the neuroprotective properties of TSG are rapidly becoming focused. Research indicated that TSG can improve the learning and memory capability of senile dementia mice and scavenge free radicals. However, whether TSG could provide protection against injury induced by PQ-MB in dopaminergic neurons or not is still unknown. The central hypothesis guiding this study is that TSG may play a protective role in PQ-MB induced injury of dopaminergic neurons and the related mechanism was detected.Experiment 1Objective: To explore the protective effect of TSG against the apoptosis of nigrostriatal dopaminergic neurons in mice induced by PQ and MB. Methods: TH immunostaining and Nissl staining were used to observe the apoptosis of nigra neurons. Results: Nissl positive neurons and TH positive neurons in control group are 287.3±7.3% and 117.5±9.3%. In TSG group, Nissl positive neurons and TH positive neurons increased. Compared with model group (104.1±9.6%), Nissl positive neurons in TSG group were reaching 113.4±7.4% (P>0.05), 174.7±6.6% (P<0.05), 266.2±10.2% (P<0.01), respectively; TH positive neurons in TSG group were reaching 63.8±6.1% (P>0.05), 75.4±5.6% (P<0.05), 109.3±7.6% (P<0.01), respectively, compared with that of model group (51.7±8.2%). Conclusion: TSG can relieve the apoptosis of dopaminergic neurons induced by PQ-MB in the nigra of mice.Experiment 2Objective: To explore the related mechanisms of the protective effect of TSG on PQ-MB induced apoptosis of dopaminergic neurons in the nigra of mice. Methods: The expression of Caspase-3 was observed by immunostaining. Results: A significant increase in the ratio of Caspase-3 positive neurons was induced after PQ-MB exposure compared with controls (P<0.01), while this activation was reduced by 40,80,160mg/kg TSG administration. The ratio of Caspase-3 positive neurons reached to 26.3±6.1% (P<0.05), 18.7±4.9% (P<0.05), 15.4±5.8% (P<0.01), respectively, compared with model group (42.5±5.2%). Conclusion: Apoptosis of dopaminergic neurons was induced by PQ and MB, and this effect could be attenuated by TSG. The possible mechanism may be through inhibiting Caspase-3 activity.
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