Translated Abstract
BackgroundParkinson’s disease (PD) is a frequent degenerative disease of central nervous system . The severe motor dysfunction, affective disorder, cognition and memory impairment are main symptoms. The major pathophysiology in substantia nigra and dopamine-contained pathway is the absence of the dopamine-contained neurons, which induces functional changes affecting the whole basal ganglia (BG) circuitry. The hyperactivity of the subthalamic nucleus (STN) in indirect pathway and the abaissement of the subthalamic nucleas in direct pathway in basal ganglia, and the restrain of cerebral ganglion. This can cause a series of clinical symptoms. The establishment of 6-hydrodopamine unilaterally lesioned rat model of Parkinson’s disease in dopamine-contained neurons system of deutocerebrum corpora striatum pathway can simulate the Parkinson’s disease pathological change in some degree. The animal models are indispensable tools for experimental study of the cause of Parkinson’s disease and centra mechanism in order to explore a new method for clinical treatment.The high expression regions of metabotropic glutamate receptor subtype 5 (mGluR5) are in striatum,hippocampus and cerebral cortex. They are G protein-coupled receptors. mGluR5 educes biological effect as the second messenger system though inositol triphosphate (IP3) and Ca2+ . mGluR5 is concerned with plasticity of neural growth in central nervous system and can strengthen inhibitory synaptic transmission of GABA-contained neurons. In corpora striatum. mGluR5 can enhance neurotoxic effect of N-methyl-D-aspartic acid (NMDA) receptors and contact with nucleus subthalamicus and dopamine system. It possibly participate the regulation of basal ganglia function and probably relate with extrapyramidal symptoms of Parkinson’s disease animal model. In hippocampus regions. mGluR5 take on long-term potentiation (LTP) effect on learning and memory.Altered expression of metabrotropic glutamate receptor subtype 5 (mGluR5) in frontal cortex, striatum and hippocampus of Parkinson’s disease model rat was not investigated in the present study. Objective:1. To explore the expression of metabotropic glutamate receptoe subtype 5 (mGluR5) in frontal cortex, striatum and hippocampus of normal rat.2. To explore the expression of metabotropic glutamate receptoe subtype 5 (mGluR5) in frontal cortex, striatum and hippocampus of PD rat.3. To investigate the altered expression of metabotropic glutamate receptor subtype 5 (mGluR5) in hippocampus of Parkinson’s disease model rat and explore the possible mechanism of long-term potentiation (LTP).4. To investigate the altered expression of metabotropic glutamate receptor subtype 5 (mGluR5) in frontal cortex and striatum of Parkinson’s disease model rat and explore the possible mechanism of motor dysfunction and neuro-protection function of antagon of mGluR5. 5. To explore the potential mechanism of the functional disturbance of frontal cortox recognition .Methods : 1. The PD rat models were established by employing 6-hydroxydopamine to lesion unilateral substantia nigral.2. All rats were divided randomly into three groups: normal group( A group), PD group ( B group ),and D-AP-5 (noncom petitive NMDA receptor antagonist ) + PD group ( C group ).Polyclonal antibody specific for mGluR5 was used to observe the immunoreaction for mGluR5 in dentate gyrus and other regions of hippocampus. Immunohistochemistry combined with the image quantitative analysis were used.3. All rats were divided randomly into three groups: normal group( A group), PD group ( B group ), and SIB-1893 ( antagonist of mGluR5) + PD group. (C group). Polyclonal antibody specific for mGluR5 was used to observe the immunoreaction for mGluR5 in frontal cortex and striatum. Immunohistochemistry combined with the image quantitative analysis were used.Results : 1. The expression of mGluR5 in the rats of A group was very high, especially in the granular layer of dentate gyrus and the pyramidal layer of CA1.Whereas an initial down regulation of mGluR5 was observed in all the regions of hippocampus of rats from B group. At the same time the expression of mGluR5 in the group of C. was increased compared to that of group B. The expression of mGluR5 was mainly on membrane. 2. The expression of mGluR5 in the rats of A group was high in the frontal cortex and striatum, Whereas an initial down regulation of mGluR5 was observed in all the regions of frontal cortex and striatum of rats from B group. At the same time the expression of mGluR5 in the group of C. was increased compared to that of group B. The expression of mGluR5 was mainly on membrane.Conclusions: 1. The expression of mGluR5 in the rats of normal group in the frontal cortex, striatum and hippocampus was very high. The expression of mGluR5 was mainly on membrane. 2. The expression of mGluR5 in the rats of PD model in the frontal cortex, striatum and hippocampus was obviously reduced compared with that of normal group. 3. The expression of mGluR5 in the rats of PD model in the hippocampus was reduced. The results guess that the hippocampus was sensitive to the effluence of Parkinson’s disease and the down-regulation of mGluR5 expression play a kind of self-protection role for the neuron. The expression of mGluR5 in the hippocampus was up-regulated by the treatment of the noncompetitive NMDA receptor antagonist D-AP-5.The results suggest that the down regulation of mGluR5 expression after the D-AP-5 may play an important role in the procedure of LTP. The mechanism of the function of mGluR5 might be NMDA receptor dependent. 4. The expression of mGluR5 in the rats of PD model in the striatum was descend. The resule suggested that a kind of patho-compensation respond maybe take place in the central nervous system after the absence of DA-contained neurone. The expression of mGluR5 in the frontal cortex and striatum was up-regulated through the use of antagonist of mGluR5 SIB-1893. The results suggest that mGluR5 may be involved in the progression of PD. The alteration in the receptor expression may be a compensatory mechanism developed after neuroprotective treatment by antagonist of mGluR5. It can reduce the indirect pathway and will be a new method for clinical treatment.5. The expression of mGluR5 in the rats of PD model in the frontal cortex was descend. The resule suggested that the frontal cortex is the area of sensitivity of PD. which the main target region of mGluR5. Probably a kind of endogenous protection system maybe take place in the central nervous system after the absence of DA-contained neurone. The expression of mGluR5 in the frontal cortex was down-regulated when mGluR5 was actived which play a protective role on neurone. mGluR5 possibly parcitipated the regulation of frontal cortex neurone. The expression of mGluR5 was up-regulated through the use of antagonist of mGluR5 SIB-1893 indicated the protective effect on neurone.
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