| Many neuroscience researches have shown that in Parkinson's disease(PD), the overactivity of glutamatergic neurons in the subthalamic nucleus (STN) activates the GABAergic neurons in the substantia nigra pars reticulata (SNr) and the internal segments of the globus pallidus (GPi). The hyperactive GPi and SNr neurons inhibit the activity of thalamocortical neurons. Then the activity of neurons in motor area and supplementary motor area is changed. These changes contribute to develop the motor symptoms of PD. A number of researches have revealed that the symptom of PD can be ameliorated by attenuating the effect of glutamate such as lesions of GPi or high frequency stimulation of the STN. Unfortunately, these surgical approaches are not widely available for its high risk. So attenuating the effect of glutamate becomes the novel pharmacological treatment strategy for PD.The metabotropic glutamate receptors (mGluRs) play important roles in diverse brain function, especially in BG and are involved in regulating synaptic transmission and cell excitability. Thus our study aims to observe and analysis the changes of expression of mGluR1αin the PD model and to discuss the role of mGluR1αin the process of PD, which might provide morphological evidence for researching novel targets for the treatment of PD.It is widely accepted that environmental toxin is involved in the etiological factor of PD. Rotenone is widely used as an insecticide in our life and production. It is a high affinity inhibitor of complex I of the mitochondria, and rotenone crosses biological membranes and blood brain barrier easily. Latterly, Sherer reported that rats who were injected with low dose rotenone subcutaneously developed the similar symptoms of PD and pathological character. Thereby, our study used rotenone as tool drug to research the effect of environmental toxin on bodies.Objective: to observe the location of mGluR1αin BG in the control group and the changed expression of mGluR1αin the rotenone group, and then to provide the experimental evidence for mGluR1αinvolved in the neurobiological changes of PD.Methods: Male Lewis rats (250g) were randomly divided into rotenone group and control group. Rotenone emulsified in sunflower oil was given subcutaneously twice a day for 50 days to rotenone group. Oil was injected as vehicle to the control group. Immunocytochemistry was used to detect the expression of mGluR1αin brain of the control group and the changes in brain of the rotenone group. Using Fluoro-Jade C staining confirm the degenerating neurons in rotenone treated rats. Western blot was used to detect mGluR1αexpression in CPu in control group and rotenone group, and the changed expression of tyrosine hydroxylase (TH) in SN and CPu.Results: 1 The toxic effect of rotenone: during the first week, the rotenone group appeared the behavior changes, such as hypokinetic, lunched posture and losing weight etc. the rate of death was higher in this time.2 The results of immunoreactivity for mGluR1αstaining: The expression intensity of mGluR1αimmuno- reactivity decreased in rotenone group. The gray scale mean value revealed that the increases were 12.98%,5.16% and 3.44% in SNr, SNc and VTA respectively compared with the control group. In other subregions such as CPu, Cg, GPe and GPi the increases were 1.69%, 3.11%, 6.37% and 7.51% respectively. There were significant differences in these regions. The value in rotenone group increased 2.16%,1.93% in AcbSh, AcbC than control group, and decreased 1.75% in CA1. However, there were no significant differences when compared the value of rotenone group in AcbSh, AcbC, and CA1 with the control group.3 Fluoro-Jade C histochemistry: The Fluoro-Jade C-positive cells and neuronal processes in SNc showed bright green fluorescence. However, the fluorescence was not detected in SNr.4 The results of Western blot: Western blot showed the ratio of relative optical density (ROD) in rotenone group decreased when compared with the control group. The ratio of ROD of mGluR1α/β-actinin in CPu in rotenone group was 0.74±0.20, which decreased 61.10% than the control group. The ratio of ROD of TH/β-actin in SN and CPu in rotenone group were 2.00±0.78 and 2.18±0.26, which decreased 51.76% and 35.97% respectively when compared with the control group.Conclusions: 1 Rotenone can change the expression of mGluR1αin rat brain, which shows the decreased expression in SNr and GPi mainly. 2 Rotenone can cause the widely neuronal degeneration in SNr, which results in TH expression decreased significantly in SN and CPu. 3 Some neurons in CPu and GP can be degenerated by rotenone. |
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