The Role Of Metabolic Glutamate Receptor 1 In The Regulation Of Synaptic Plasticity Induced By Al?mal?₃ In Rats

Objective: To investigate the damage of synaptic plasticity in rats,and the regulatory role of m Glu R1 to the changes in synaptic plasticity in rats exposed with maltol aluminum(Al(mal)3).Methods: The fiftty-four healthy adult male SD rats,with no specific pathogens,were feed in animal laboratory of Shanxi Medical University.The rats underwent lateral ventricular intubation surgery,and postoperative week according to the weight were randomly divided into 9 groups: the operation control group(only lateral ventricle intubation surgery),saline control group(injected with saline 5 ?L),Al(mal)3 group(4,16,64 mm Al(mal)3,5 ?L),the m Glu R1 agonist group(0.1 ?M DHPG,5 ?L),the m Glu R1 antagonist group(0.2?M MCPG,5?L),Al(mal)3+m Glu R1 agonist group(16m M/3?L Al(mal)3+ 0.1?M/2?L DHPG),Al(mal)3+m Glu R1 antagonist group(16m M/3?L Al(mal)3+0.2?M/2?L m Glu R1 MCPG).Treatment aforementioned was performed every 2 days and continued for 10 days.After the Al(mal)3 exposure,Y maze was used to test the spatial memory and learning ability of the rats.Field excitatory postsynaptic potential(f EPSP)in hippocampus CA1 was recorded by field potentiation technique in vivo.The m RNA expression of m Glu R1,PKC,PKC? and NMDAR subunits in the hippocampus were detected by RT-q PCR.Western Bloting was used to detect the protein levels of m Glu R1,PKC,PKC? and NMDAR subunits,and the phosphorylation levels of NMDAR1 and NMDAR2 B.Results: 1.Effects of Al(mal)3 on inhibition of hippocampal synaptic plasticity and related protein expression in rats Y maze test results showed that compared with the operation control group,there was no significant change in the spontaneous alternations rate(SAP)of the normal saline control group(P>0.05).Compared with the saline control group,SAP of the 16 m M Al(mal)3 group deduced by 20.5%(P<0.05).In vivo electrophysiological examination showed that there was no statistical difference between the saline control group and operation control group at all time points(P>0.05).At the same time point,compared with the saline control group,the average amplitude of f EPSP decreased with the increase of the dose of Al(mal)3(P<0.05).In the same treatment group,compared with 0min,the average amplitude of f EPSP decreased with the prolonging of recording time(P<0.05).The PCR results showed that compared with the operation control group,the m RNAs expression of saline control group has no obvious difference(P >0.05);compared with saline control group,the m RNA expression of m Glu R1 increased by 56.9%,the m RNA expression of PKC,NMDAR1 and NMDAR2 A decreased by 29.7%,45.5% and 43.4% respectively,the differences were statistically significant(P<0.05).The Western Blot results show that compared with the operation control group,the proteins expression of saline control group has no obvious difference((P>0.05);compared with the saline control group,the protein expression of m Glu R1 increased by 51.9%,the protein expression of PKC,NMDAR1,NMDAR2 A and NMDAR2 B decreased by 24.5%,45.6%,18.3% and 36.4% respectively,the differences were statistically significant(P<0.05).2.The regulatory role of m Glu R1 in the damages of synaptic plasticity in rats treated with Al(mal)3.(1)Y maze test showed that compared with Al(mal)3 group,SAP of rats in Al(mal)3+DHPG group decreased,while that of rats in Al(mal)3+MCPG group increased(P<0.05).In vivo electrophysiological test results showed that at the same time point, compared with Al(mal)3 group,the average amplitude of f EPSP decreased in group DHPG+Al(mal)3,while the average amplitude of f EPSP increased in group MCPG+Al(mal)3.PCR showed that compared with Al(mal)3 group,in DHPG+Al(mal)3 group,the m RNA expression of m Glu R1 increased,while the m RNA expression of NMDAR1 and NMDAR2 A decreased(P<0.05);in MCPG+Al(mal)3,the m RNA expression of m Glu R1 group decreased,while that of NMDAR1 and NMDAR2 A increased(P<0.05);NMDAR2B m RNA and PKC m RNA expression showed no significant difference(P>0.05).Western Blot showed that compared with Al(mal)3 group,in DHPG+Al(mal)3 group,the protein expression of m Glu R1 increased,while the protein expression of NMDAR1,NMDAR2 A and NMDAR2 B decreased(P<0.05);in MCPG+ Al(mal)3 group,the protein expression of m Glu R1 decreased,while the protein expression of NMDAR1 and NMDAR2 B increased(P<0.05);there was no significant difference in PKC protein expression(P>0.05).(2)Compared with the saline control group,the expression of PKC? m RNA and protein in Al(mal)3 group decreased(P<0.05).Compared with Al(mal)3 group,the expressions of PKC? m RNA and protein in DHPG+ Al(mal)3 group decreased,while that in MCPG+ Al(mal)3 group increased(P<0.05).(3)Compared with saline control group,the expression of p NMDAR1 and p NMDAR2 B in Al(mal)3 group decreased(P<0.05).Compared with Al(mal)3 group,the expressions of p NMDAR1 and p NMDAR2 B in DHPG+ Al(mal)3 group decreased,while that in MCPG+ Al(mal)3 group increased(P<0.05).Conclusions: 1.Al(mal)3 can inhibit synaptic plasticity in rats,and the damage is aggravated with the dose increase of Al(mal)3.2.Al(mal)3 can increase the expression of m Glu R1,and inhibit the expression of PKC,NMDAR1 and NMDAR2 A at the transcription and translation processes,while the inhibition of NMDAR2 B is at the translation process.3.The inhibition of Al(mal)3 on synaptic plasticity may be related to the inhibition of m Glu R1 on PKC and NMDAR1 expression and the inhibition of phosphorylation of NMDAR1 and NMDAR2 B.