deletion of rage causes hyperactivity and increased sensitivity to auditory stimuli in mice删除的愤怒会导致多动症和对小鼠的听觉刺激敏感性增加.pdfVIP

Deletion of RAGE Causes Hyperactivity and Increased Sensitivity to Auditory Stimuli in Mice 1. 2. 2 3 3 Seiichi Sakatani , Kazuyuki Yamada , Chihiro Homma , Seiichi Munesue , Yasuhiko Yamamoto , Hiroshi Yamamoto3, Hajime Hirase1,4* 1 Hirase Research Unit, RIKEN Brain Science Institute, Wako, Saitama, Japan, 2 Research Resource Center, RIKEN Brain Science Institute, Wako, Saitama, Japan, 3 Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan, 4 Saitama University Brain Science Institute, Saitama, Japan Abstract The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor that belongs to the immunoglobulin superfamily of cell surface receptors. In diabetes and Alzheimer’s disease, pathological progression is accelerated by activation of RAGE. However, how RAGE influences gross behavioral activity patterns in basal condition has not been addressed to date. In search for a functional role of RAGE in normal mice, a series of standard behavioral tests were performed on adult RAGE knockout (KO) mice. We observed a solid increase of home cage activity in RAGE KO. In addition, auditory startle response assessment resulted in a higher sensitivity to auditory signal and increased prepulse inhibition in KO mice. There were no significant differences between KO and wild types in behavioral tests for spatial memory and anxiety, as tested by Morris water maze, classical fear conditioning, and elevated plus maze. Our results raise a possibility that systemic therapeutic treatments to occlude RAGE activation may have adverse effects on general activity level