| Parkinson's disease(PD)is a neurodegenerative disease common in the elderly,which has a serious affect on the life of patients.The prevalence of PD was 1-2%in the population aged over 60,which increased with the age.But the etiology and pathogenesis of PD has not been fully elucidated.In recent years,It has made a breakthrough on the research of PD with the use of animal models,and it wil give more insight into the study of the pathogenesis process,etiology and molecular mechanism of PD.The earliest model of PD disease was the using of reserpine,then was methamphetamine,6-OHDA,MPTP,rotenone etc.Which 6-OHDA PD model and MPTP PD model were mostly used.The PD model of rotenone,a new type of induced drug,shows a number of characteristics of sporadic Parkinson's disease.The PD animal model based on genetic and environmental toxinshas great significancein revealing the molecular mechanisms on the death of dopaminergic cells and identifying potential therapeutic targets.In our paper,we set up a model of silkworm Parkinson's disease induced by rotenone.The results were as follows:1.The evaluation of virulence and sublethal dose of silkworminduced by rotenoneFeeding with different concentration of rotenone to the silkworm,we identified the virulence and sublethal dose of silkworm,respectively 0.473mg/kg/days and 0.610mg/kg/days.2.Sublethal dose effects of rotenone on athletic ability of silkwormWith the dyskinesia,such as unstable and difficulty in bending,the weight and survival rate of silkworm significantly decreased after feeding with 0.4 mg/kg and 0.2 mg/kg rotenone everday since L2D1.3.The rotenone cause the damage on the brain dopaminergic neuron of silkwormThe qRT-PCR shows that the expression of key enzyme for dopamine biosynthesis of silkworm brain,such as tyrosine hydroxylase(TH)and dopa decarboxylase(DDC),reduced significantly after 20 days by fed with rotenone;The high performance liquid chromatography(HPLC)shows a decreased on dopamine;And the immunohistochemistry reveals that the expression of the neurons molecular markers(TH)significantly reduced onbrain dopaminergic.4.The selective damage of rotenone on brain dopaminergic neuronsThe high performance liquid chromatography(HPLC)reflects that the content of brain serotonin and acetylcholine has little changes,which proved that acetylcholine neurons and serotonin neurons relatively unaffected by rotenone;Tunel staining found that thesize and morphology of silkworm brain have no significant difference,Then We draw the following conclusions:the sublethaldose of rotenone has a selective damage on brain dopaminergic neurons.5.Rotenone cause the oxidative stress and mitochondria damage on the brain of silkwormWe found the content of active oxygen and lipid oxidation on silkworm brain significantly increased and the content of glutathione and superoxide dismutase(SOD)decreased significantly after rotenone induced;Namely that rotenone can disorder the oxidative stress of silkworm.At the same time,we found by the ATP levels and mitochondrial membrane potential(??m)decreased significantly,which indicted that rotenone damage the mitochondria in silkworm brain.Also,the expression of DJ-1 and UB mRNA,the autophagy related protein ATG5 and ATG8 increased significantly.These explained the oxidative stress and mitochondria damage is closely associated with Parkinson's disease.6.The effection of anti-Parkinson drug Levodopa on the pathological phenomena of silkwormafter induced by rotenoneThe athletic ability of silkworm improved significantly after fed with 1 mg/kg levodopa,but there has no significant changes in the expression of dopamine and TH protein.Namely,levodopa can only improve the dyskinesia,nor protect the dopaminergic neuron damage induced by rotenone. |
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