The Effect Of PBDE 209 Exposure On The Spatial Learning And Memory,the Expression And Phosphorylation Of Hippocampal Glutamate Receptors In Adult Rats

Objective: This study was aimed to investigate the effect of PBDE-209 exposure on the spatial learning and memory,the expression of hippocampal glutamate receptor subunits NR1,NR2 B and Glu R1,the phosphorylation of NR2 B subunit at Ser1303 and Glu R1 subunit at Ser1303,and then explore the potential mechanism underlying the spatial learning and memory deficit induced by PBDE-209 exposure.Methods: Thirty-two 10-week old healthy male Sprague Dawley rats were divede into four groups randomly,included one vehicle control group and three PBDE-209 treated groups(low,medium and high dose groups),each group contained 8 rats.The vehicle control group and PBDE-209 treated groups were administered with vehicle(peanut oil)and PBDE-209 emulsion(250,500 or1000 mg/kg)respectively.The treatment was conducted for 30 consecutive days and once daily by gavage.The spatial learning and memory was evaluated in the Morris water maze.The expression of glutamate receptor subunits NR1,NR2 B and Glu R1,the phosphorylation of NR2 B subunit at Ser1303(p-NR2 B Ser1303)and Glu R1 subunit at Ser831(p-Glu R1 Ser831),the expression of αCa MKII and phosphorylation at Thr286 were detected using western blotting method.The phosphorylation ratio of NR2 B and Glu R1 subunits were described as p-NR2B/NR2 B and p-Glu R1/Glu R1 respectively.Results: 1.The results of Morris water maze test:(1)During the hidden platform trial,all rats’ escape latencies were decreased during the 4 days’ training(P<0.05).However,escape latencies of rats in medium and high dose groups were significantly longer than control and low dose groups(P<0.05).Also,escape latencies of rats in high dose group were significantly longer than medium dose group(P<0.05).(2)During the probe trial,rats in medium and high dose groups showed less frequencies to enter the target quadrant and cross the original platform,shorter swimming distance and time-spend in the target quadrant than control and low dose groups(P<0.05),so did high dose group when compared with medium group(P<0.05).2.The results of western blotting:(1)When compared with control group,significantly inhibited expression of the hippocampal glutamate subunits NR1,NR2 B and Glu R1 in three PBDE-209 treated groups were observed(P<0.05).Also,the decreased expression of hippocampal NR2 B and Glu R1 subunits in medium and high dose groups were also observed when compared with low dose group.(2)The levels of p-NR2 B Ser1303 and p-Glu R1 Ser831 were significantly decreased in the hippocampus of rats in three PBDE-209 treated groups than controls(P<0.05).Also,the level of p-Glu R1 Ser1303 in the hippocampus of rats in medium dose group was significantly decreased than low dose group(P<0.05),the level of p-Glu R1Ser1303 in the hippocampus of rats in high dose group was significantly decreased than medium dose group(P<0.05).Moreover,the phosphorylation ratio of NR2 B subunit in the hippocampus of rats in medium and high dose groups were significantly increased than control and low does groups(P<0.05).However,the phosphorylation ratio of Glu R1 subunit showed no significant difference between groups(P>0.05).(3)The expression of hippocampalαCa MKII and the phosphorylation at Thr286 were significantly inhibited in three PBDE-209 treated groups when compared with control group(P<0.05),and the expression of hippocampal αCa MKII and the level of p-αCa MKII Thr286 in high dose group were significantly decreased than low dose group(P<0.05).Conclusion: 1.PBDE-209 exposure could induce spatial learning and memory deficit in adult rats.2.PBDE-209 exposure could inhibit the expression of hippocampal glutamate receptor subunits NR1,NR2 B and Glu R1,decrease the phosphorylation of NR2 B subunit at Ser1303 and Glu R1 subunit at Ser831 and increased the phosphorylation ratio of NRB subunit in adult rats,the expression of αCa MKII and phosphorylation at Thr286 were also inhibited.3.The changes in the expression and phosphorylation of hippocampal glutamate receptor subunits and αCa MKII might be a potential mechanism underlying the spatial learning and memory deficits induced by PBDE-209.Moreover,the alterations of the expression and phosphorylation of αCa MKII might be partly associated with the change of the phosphorylation of glutamate receptor subunits.