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《Molecular Neurobiology》 1:8月18日 (2015)

Maged1 Co-interacting with CREB Through a Hexapeptide Repeat Domain Regulates Learning and Memory in Mice

Yang, JianJun; Lai, BeiBei; Xu, AiLi; Liu, Yu; Li, XiaoMin; Zhao, YongNa; Li, WeiFeng; Ji, MuHuo; Hu, Gang; Gao, Xiang; Gao, Jun

Abstract:

Maged1 is a member of the type II melanoma antigen (MAGE) family of proteins, which is highly conserved in the brain between mouse and human. Recently, Maged1 has been reported to be involved in depression and impaired sexual behavior. However, the role of Maged1 in learning and memory remains unknown. The aim of the present study was therefore to investigate whether Maged1 deficiency can impair learning and memory formation. By behavioral tests and electrophysiological recording, we observed that 5–6-month-old Maged1 knockout mice displayed the reduced basal synaptic transmission, pronounced hippocampal dysfunction, impaired spatial learning, and a deficit in long-term potentiation induction. Data from immunohistochemical andWestern blot showed the reduced dendritic spine density and the number of synapses in the hippocampus of the Maged1 knockout mice, and Maged1 deficiency prevented the interaction of Maged1 with cAMP response elementbinding protein (CREB). Furthermore, by chromatin immunoprecipitation and luciferase assay, we observed the downregulated activity of CREB and the suppressed CREBdependent transcription after deficiency of Maged1, which lead to the decreased levels of brain-derived neurotrophic factor. Taken together, our results provide the evidence that Maged1 is involved in synaptic transmission and hippocampus-dependent learning and memory formation.