| Objective:To observe the changes about pathohistology and neurobehavior of the mice induced by aluminium and to study the role of metabotropic glutamate receptors (mGluRs) and NMDAR in the damage of learing and memory induced by aluminium.Methods:40 maleness C57BL mice,adult and health,were divided into 4 groups randomly, 10 in each group, 3 exposed groups and the vehiculum control group . The exposed groups were treated by lateral cerebral ventricle micro-injection with Aluminiumchlorid dissolved in artificial cerebrosninal flu(ACSF) at 1,0.5 and 0.25mg/ml respectively,one time every day,for 5days,the vehiculum control group was given ACSF. .After 12 days exposure, the step-down test, the passive avoidance test and the Morris water maze test were performed to test the learning and memory abilities of mice. Then sudden death the mice, s1ices of the cerebral cortex hippocampus was made and morphological changes were observed by optical microscope. Expression of NMDAR1 and NMDAR2B in neural cells in mice'brain tissue were measured with ABC of immunohistoc-hemical method. mGluR1,mGluR3,mGluR7,NMDAR1 and NMDAR2B in brain tissue were detected with methods of RT-PCR and Western-blotting ECL, and the results were analyzed with Gelatum Analyzing System;Results:learning and memory capability test: 1) In Step-down Test, it was showed that compared with the ACSF control group,the latency(LT) was shortened (P<0.05) in the low-dose group. both EN1 and EN2 decreased (P<0.05)and the LT was shortened (P<0.05) in the medium -dose group, both EN1 and EN2 increased (P<0.05) and the LT was shortened obviously (P<0.01) in the high-dose group;2) In the Passive avoidance Test, it was showed that compared with the ACSF control group: the EN2 increased (P<0.05) in the low–dose group, and the LT were shortened(P<0.05),the EN2 increased significantly (P<0.01) in the medium-dose, the LT were significantly shortened (P<0.01),the EN2 increased significantly (P<0.01) in the high-dose groups;3)In the Morris water maze test,it was showed that compared with the ACSF control group,in the place navigation test, the LT was shortened(P<0.05) in the medium-dose and high-dose groups,in the spatial probe test, the number of times passing over hidden platform and the retention time significantly decreased (P<0.01),the swimming distance through the quadrant of hidden platform were shortened(P<0.05) in the medium-dose and high-dose groups. Pathohistology results:in control group the morphosis of mice hippocamp pyramidal layer neuron is basically normal,lining up in order, but with the increasing of the doses of Al3+ exposed, the neurocytes displayed disorderly, the cell junction get loose,, the karyon shrinked,some rings around the neurocyte were observed. Immunohistochemical results: plenty of immune reaction positive neurons can be seen in hippocamp pyramidal layer, NMDAR1 and NMDAR2B positive reaction is located in cell membrane. With the higher Al3+ exposed, the higher immune reaction positive neurons. The analysis of RT-PCR and Western- blotting ECL showed that: compared with the ACSF control group,the express of gene and proteinum of mGluR1 is no marked change( P> 0.05)in low-dose group, and the express of gene and proteinum of mGluR1 is increase(P<0.05) in the medium -dose and high group; Compared with the ACSF control group,the express of gene of mGluR3 was decrease(P<0.05) and express of proteinum was no marked change( P> 0.05)in every group; Compared with the ACSF control group, the express of gene of mGluR7 was no marked change( P> 0.05)in low-dose group, the express of gene of mGluR7 was significantly decrease (P<0.01), and the express of proteinum was decrease(P<0.05) in the medium -dose and high group; Compared with the ACSF control group,the express of gene and proteinum of NMDAR1,NMDAR2B was no marked change( P> 0.05)in low-dose group.The express of gene and protein of NMDAR1 were increase(P<0.05) and the express of protein of NMDA2B was increased (P<0.05) in the medium -dose group; In the high-dose group, the express of gene of NMDAR1 were increase (P<0.05) and the NMDA2B was significantly increased (P<0.01), the express of protein of NMDAR2B were increase(P<0.05) and the NMDA1 was significantly increased (P<0.01).Conclusion: Aluminium could induce learning and memory disorder in mice, and induce the morphosis changes of mice hippocamp pyramidal layer neurons. And the changes get more obviously with the augment of dosage. The pathomechanism of Aluminium-induced damage of learning and memory could be involved in the high expression of mGluR1,NMDAR1,NMDAR2B. |
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