Inhibition of GluA2-containing AMPA receptor endocytosis improves motor and cognitive functions in a rat model with traumatic brain injury
Objective:To investigate the effects of inhibition of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropi-onic acid receptor(AMPAR)endocytosis on motor and cognitive functions in a rat model with traumatic brain injury(TBI)and related mechanisms.Methods:The model rats with moderate TBI were established and divided into the Sham group(with open cranial window only),saline group(treated with normal saline),scr-GluA23Y group(treated with the control peptide scrambled Tat-GluA23Y),and G1uA23Y group(treated with the test peptide Tat-GluA23Y).The improvement in motor and neurological functions of rats was measured by the Mahmood's method neurological severity score(mNSS)and grip strength test.Then,the exploration ability and spatial learning and memory ability of rats were assessed by the new object experiment and water maze experiment.The change in AMPAR expression of synaptic and total proteins in the hippocampus was measured by Western blot.Results:The mNSS and grip strength test showed that the neurofunction status(P=0.013)and grip strength(P＜0.001)of the GluA23Y group improved significantly over time compared with the saline group.The new object experiment showed that the number of contacts(0.60±0.02,P＜0.01)and contact time(0.57±0.03,P=0.011)of the GluA23Y group were significantly increased compared with the scr-GluA23Y group(P＜0.01,P=0.010).The wa-ter maze experiment results showed that the learning(P＜0.001)and memory ability(P=0.037)were improved in the GluA23Y group(21.43±1.76)compared with the scr-GluA23Y group.Western blot revealed that the content of GluA 2 in the hippocampus was specifically increased after treatment with GluA23Y(0.98±0.03,P=0.981 vs.Sham,P=0.025 vs.saline,P=0.025 vs.scr-GluA23Y).Conclusion:AMPAR endocytosis inhibitors,such as Tat-GluA23Y,repair the impaired motor and cognitive function induced by TBI by increasing the content of GluA2 in the rat hippocampus.
traumatic brain injuryα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosislearning and memoryhippocampus
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维普
