Beneficial Effects Of Inhibiting Hippocampal NgR On Learning And Memory In Diabetic Rats

ObjectiveNogo Receptor(NgR)is a receptor for myelin-associated axon growth inhibitors.This study aims to investigate the effect of NgR on learning and memory in diabetic rats and its possible mechanisms.MethodsSprague-Dawley rats were randomly divided into 4 groups: control group,diabetic group,siNgR group and siRNA group(n=10 in each group).Except for the control group,other groups were intraperitoneally injected with streptozotocin(60 mg/kg)to establish diabetic models.After diabetes onset,control and diabetic groups were then injected with virus preservation solution(10 ul)into bilateral sides of the hippocampus,AAV�packed NgR antisense nucleotide sequence(10 ul)was injected in the siNgR group.AAV-packed silenced nucleotide sequence(10 ul)was injected in the siRNA group.Morris Water Maze was used to detect the learning and memory ability of each groups.The protein expression of hippocampal NgR,Synaptophysin(SYP)were detected by immunofluorescence stain.Western blotting was used for the detection of NgR,SYP and Growth associated protein-43(GAP-43)protein expression in hippocampus.ResultsNissl staining showed that the brain stereotactic injection was successfully injected into the hippocampus of each group.Immunofluorescence staining and Western blotting showed that relative expression of hippocampal NgR in the diabetic group and the siRNA blank group was significantly increased compared with the control group(P<0.05).Compared with the diabetic group,relative expression of hippocampal NgR in the siNgR group was significantly reduced(P<0.05).It is suggested that the siNgR nucleotide sequence successfully inhibits hippocampal NgR expression of diabetic rats.During the acquisition training phase,the escape latency of the control group,the diabetic group,the siNgR group,and the siRNA blank group were(9.0�1.9)-s,(32.2�10.6)-s,(18.8�8.9)-s,and(32.5�9.1)-s,The results showed that compared with the control group,the escape latency of the diabetic group and the siRNA blank group was significantly prolonged(P<0.05).Compared with the diabetic group,the escape latency of the siNgR group was significantly shortened(P<0.05).In probe trials,the time of the control group,the diabetic group,the siNgR group,and the siRNA blank group spent in the target quadrant where the platform was located were(31.3�3.7)-s,(19.8�6.2)-s,(27.2�5.5)-s,and(19.3�3.5)-s.Results showed that the time of the diabetic group and the siRNA blank group was significantly shorter comparing with the control group(P<0.05),Compared with the diabetic group,the rats in the siNgR group were significantly prolonged in the quadrant where the platform was located(P<0.05).Immunofluorescence staining and Western blotting analysis showed that compared with the control group,relative expression of SYP in the diabetic group and the siRNA blank group was significantly decreased(P<0.05),relative expression of GAP-43 was significantly elevated(P<0.05).Compared with the diabetic group,the relative expression of SYP in the siNgR group was significantly increased(P<0.05),and the relative expression of GAP-43 was further increased(P<0.05).ConclusionsInhibition of NgR in the hippocampus can improve the learning and memory ability of diabetic rats,which may be related to the up-regulation of GAP-43 and SYP expression.