Impaired long-term potentiation and hippocampus-dependent memory formation in AQP4 knockout mice is rescued by GLT-1 activation

【摘要】：正OBJECTIVE Although the role of newly identified aquaporin 4(AQP4) in water transport has been extensively investigated, little is known about its contribution to hippocampal synaptic plasticity and memory.Since it has been detected widely co-localized with glutamate transporter 1(GLT-1 ) in astrocytes, we thus investigated whether AQP4 was implicated in long-term potentiation(LTP) and memory formation via GLT-1. METHODS Using tissue immunofluorescence double staining to measure coexpression of AQP4 and GLT-1.WB was employed to detect the expression of GLT-1.In vivo electrophysiological recording method was established to record the PS,and TBS was developed for the induction of LTP.Contextual fear conditioning test was used to evaluate hippocampus-dependent memory.Golgi impregnation indicated the density of dendritic spines.Results; Our present study demonstrated that AQP4 deficiency impaired hippocampal LTP and hippocampus-dependent memory formation and this impairment was mediated by the down-regulation of GLT-1 expression/function in hippocampus in AQP4 knockout (KO) mice,since it could be rescued by ceftriaxone(Cef),a stimulator of GLT-1.CONCLUSION These results suggest that AQP4 functions as the modulator of synaptic plasticity and actively regulates learning and memory.