Metabotropic Glutamate Receptor Expression In Memory Impairment In Mice Induced By Aluminum,

Objective This study was performed to study the pathohistology and neurobehavior changes of the mice induced by aluminium and to observe the expression of metabotropic glutamate receptors(mGluRs) in the merory damage caused by aluminium.Methods 30 Kunming mice,half male and half female,were'divided into 3 groups randomly according to their weight,10 in each group.They were injected normal saline, 0.5%AlCl₃,1.0%AlCl₃ 3μl respectively to lateral cerebral ventricle for 5consecutive days.8 day later,Water maze,platform jump and darkness avoidane experients were performed to testify the learning and memory capability of the animals.Then the mice were killed,and cerebral cortex,double side hippocamp were isolated to observe the change of mice's histology.Immunohchemical methed'was used to detect the distribution of the positive cells of cerebral cortex and hippocamp.30 Kunming mice,half male and half female,were divided into 3 groups randomly acorrding to their weight,10 in each group,keep injecting normal saline with 0.5% AlCl₃+,0.5mgAlCl₃+cppg,0.5%AlCl₃+lap4 each for 3μl and 2μl respectively to lateral cerebral ventricle for 5 consecutive days.8 day later,Water maze,platform jump and darkness avoidane experients were performed to testify the learning and memory capability of the animals.Then the mice were killed,and cerebral cortex,double side hippocamp were isolated to observe the change of mice's histology.Immunohchemical methed was used to detect the distribution of the positive cells of cerebral cortex and hippocamp.Results Histopathological results:HE staining:In control group,the morphosis of mice hippocamp pyramidal layer neuron was basically normal,lining up in order.The alignment of cells became in disorder with greater dosage of Aluminium.In higher dosage group,cell junction got loose,endochylema condensed,anachromasis,karyopyknosis of shrinking somas and ring belt appeared around the cells.The amount of the zone without dye,and the cells were increased.The changes of their neurobehavior were also significant.Compared with the control group,the latency of entering the daek chamber was abviously shortened(P＜0.05),and the number of the mistakes increased remarkly(P＜0.05).These results suggested AlCl₃ could damage the memory ability of passive avoidance in mice.In spatial probing,compared with the control group,the time of target quadrant stasis decreased apparently(P＜0.05),and the latency of finding the platform of 0.5%AlCl₃ group increased significantly(P＜0.05).And after the addition of excitomotor Lap4,compared with 0.5%AlCl₃+NaCl group, the latency of platform jump of 0.5%AlCl₃+ Lap4 group increased significantly(P＜0.05), and the number of the mistakes decreased remarkly(P＜0.05).The latency of darkess aviodance prolonged,while the number of the mistakes decreased notably.The latency of finding the platform shortened significantly(P＜0.05),the time of target quadrant stasis in spatial probing prolonged.After adding the excitomotor Cppg,compared with 0.5% AlCl₃+NaCl,the stage of latency of 0.5%AlCl₃+ +Cppg group decreased significantly (P＜0.05),and the number of the falut increased remarkly(P＜0.05).The latency of darkess avoidance shortened,while the number of the falut increased somewhat.The latency of finding the platform and the time of target quadrant stasis in spatial probe shorten had not change significantly.Compared with control group,western blot showed there were no obvious changes in the mGluRs1 expression in experiment group(P＞0.05),but the expression of mGluRs3 and mGluRs7 increased obviously(P＜0.05).Immunohistochemical results:with Image-Pro plus 6.0 image analysis software, plenty of mGluRs immune reaction positive neurons can be seen in hippocamp pyramidal layer.Positive reaction is located in cell intracytoplasm,display buffy.The amount of positive neurons in experiment group is greater than in control group(P＜0.05).The amount of positive neurons in 1.0%Al³⁺ group is greater than in 0.5%Al³⁺ group.With agonist and antagon,the average optical density of 0.5%Al³⁺+ Lap4 group decreased significantly compared with 0.5% Al³⁺ group(P＜0.05),but the average optical density of 0.5%Al³⁺+Cppg group increased compared to 0.5%Al³⁺ group.Conclusion Aluminium could cause the morphosis changes of mice hippocamp pyramidal layer neurons.And the changes get more obvious with the increase of the dosage.Aluminium could induce the neurobehavioral changes of mice and produce obstacle for learning and memory.The pathomechanism of Aluminium-induced damage of learning and memory was probably related with the expression of mGluRs3 and mGluRs7.