Journal Article

A new coumarin derivative, IMM-HOO4, attenuates okadaic acid-induced spatial memory impairment in rats

Xiu-yun SONG Ying-ying WANG Shi-feng CHU Jin-feng HU Peng-fei YANG Wei ZUO Lian-kun SONG Shuai ZHANG Nai-hong CHEN

2016

Overview

Aim： A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-（4-methylpiperazin-l-yl）-coumarin （IMM-HO04） has shown antiapoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-HOO4 on spatial memory in rats treated with okadaic acid （OKA）, which was used to imitate Alzheimer＇s disease （AD）-Iike symptoms. Methods： SD rats were administered IMM-HOO4 （8 mg.kg-1d-1, ig） or donepezil （positive control, 1mg.kg-1.d-1, ig） for 25 d. On d 8 and 9, OKA （200 ng） was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and 13-amyloid （Aβ） pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. Results： OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-HO04 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aβ protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-HOO4 or donepezil. Conclusion： Administration of IMM-HO04 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aβ pathology. Thus, IMM-HOO4 may be developed as a therapeutic agent for the treatment of AD.

• Subject: Morris水迷宫 / SD大鼠 / tau蛋白 / 淀粉样蛋白 / 记忆障碍 / 评价空间 / 诱导空间 / 香豆素衍生物