| Parkinson's disease(PD) also known as Paralysis agitans is a progressiveneuro degenerative disease which is most common.The changes of PD arethe loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal proteinacious cytoplasmic inclusions,termed"Lewy Bodies,(Lewy's).But the reason for the change of pathological mechanisms is not clear.Amongthe many studies such as:genetic factor,environmental agent,oxidativestress,excitotoxicity,immunology abnormality and the correlation with the PDare widely recognized.Glutamate is considered as the major excitatory neurotransmitter in thecentral nervous system. While many pathology factors can lead to the Glu byelevated extracellular, and the concentration of glutamate may causeneurotoxicity. The relation between it and neurodegeneration such as PD ispaid much attention. Meanwhile more and more human as the breakthroughpoint to study and research the prevention and therapy of PD. A number ofresearches have revealed that the symptom of PD can be ameliorated byattenuating the effect of glutamate such as lesions of GPi or high frequencystimulation of the STN. Unfortunately, these surgical approaches are notwidely available for their high risk. So the pharmacotherapy is the preferredtreatment measure for PD. L-dopa,LD is the commonly used medicine,however, the efficacy significantly decreased of the long-term medicationcausing side effects, such as: motor fluctuations and dyskinesia. So this essayaims to study how to reduce the effect of glutamate or to search for newstrategies to treat PD by other neuro protective organization.Rotenone is a widely used insecticide in our life and production. It is ahighly affinity inhibitor of complex I of the mitochondria, to lead torespiration defect, and rotenone crosses biological membranes and blood brain barrier easily. Latterly in the central nervous system dopaminergic neurons isso saitivity reported that rats who were injected with low dose rotenonesubcutaneously developed the similar symptoms of PD and pathologicalcharacter.。It may have a relationship with the disturbance of glutamatetransport system in astocytes. However, the mechanism of rotenone in PD isunclear. Thus, studies in the mechanism of rotenone-induced PD in molecularlevel is helpful for understanding PD.The main aim of this study is to elicit the molecular mechanism ofrotenone-induced neurodegeneration based on the researches on Glutransporters and gluatamate receptor. Thus our study aims to observe andanalysis the changes of expression of mGluR1αin the PD model and to discussthe role of mGluR1αin the process of PD, which might provide morphologicalevidence for researching novel targets for the treatment of PD..Objective: SD rats were administrated with rotenone,to observe thelocation of mGluR1α and GLT-1in brain in the control group and the changedexpression of mGluR1α and GLT-1in the rotenone group, and then to providethe experimental evidence for mGluR1a and GLT-1involved in theneurobiological changes of PD.Methods: Male SD rats (300g) were randomly divided into rotenonegroup and control group. Rotenone emulsified in sunflower oil was givensubcutaneously twice a day for3day and28days to rotenone group. Oil wasinjected as vehicle to the control group. Immunocytochemistry was used todetect the expression of mGluR1α and GLT-1in brain of the control group andthe changes in brain of the rotenone group.Western blot was used to detect thechanged expression of tyrosine hydroxylase (TH) in SN.Results:1The toxic effect of rotenone:starting from the fifth day, the behavior changesappeared in the rotenone group, such as: Coat color gradually turn yellow,dirty and chaos,respond dull,lethargy, hypokinetic,posture,limb tremor,smell and decreased appetite and losing weight etc. Thus the rate of death washigher during this time. 2The results of Western blot: Western blot showed the ratio of average opticaldensity (AOD) in rotenone group decreased when compared with the controlgroup. The ratio of AOD of TH/β-actin in SN in rotenone group were0.189±0.026,which was decreased by66.5%respectively when comparedwith the control group.3The results of immunoreactivity(1)The results of immunoreactivity for mGluR1α staining:showed the ratioof average optical density (AOD) in rotenone group decreased when comparedwith the control group. The ratio of AOD of DM,VM,VL,DL mGluR1α inCPu in rotenone group decreased by23.35%,21.93%,15.59%and43.28%,respectively when compared with the control group statistically significant.The ratio of AOD of Acb decreased by4.89%respectively when comparedwith the control group not statistically significant.(2)The results of immunoreactivity for GLT-1staining:1) The ratio of AOD of DM of GLT-1in CPu in3days rotenone groupdecreased by0.8%. The ratio of AOD of VM,VL,DL of GLT-1in CPu in3days rotenone group increased by5.9%,16.8%and14%, only VLrespectively when compared with the control group statistically significant.The ratio of AOD of Acb decreased by7.5%respectively when compared withthe control group not statistically significant.2)showed the ratio of AOD in rotenone28days group increased whencompared with the control group. The ratio of AOD in DM,VM,VL,DL ofGLT-1in CPu in rotenone group increased by24.39%,34.19%,41.58%and47%, respectively when compared with the control group statisticallysignificant.3) the ratio of AOD in28days group increased when compared with the3days group. The ratio of AOD of DM,VM,VL,DL of GLT-1in CPu in28days group increased by25.41%,26.61%,21.17%and28.95%,respectivelywhen compared with the3days group statistically significant. The ratio ofAOD of Acb increased by15.31%respectively when compared with thecontrol group not statistically significant. Conclusion:1Retenone has obvious neurotoxicity, and it can cause the loss of nigrostriataldopaminergic neurons in rats' brains, thus appearing some symptoms similarto PD.2Rotenone can change the expression of mGluR1α in rats' brains, which wasmainly shown in the decreasing of the expression in Cpu.3The expression intensity of GLT-1immuno-reactivity increased in rotenonegroup and the expression will strengthened as the increase of time of offeringmedicine. |
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