AM251型
认知灵活性
大麻素
内分泌学
灵活性(工程)
大麻素受体
内科学
雌激素
内大麻素系统
认知
医学
小发夹RNA
受体
敌手
药理学
生物
神经科学
基因敲除
基因
统计
数学
生物化学
作者
Fu Sheng Yang,Yingjie Zhao,Sijie Chen,Yaru Li,Pei-Yue Yang,Jing-yu Qi,Xin‐shang Wang,Min Wang,Xubo Li,Bo Feng,Yumei Wu,Shui-bing Liu,Kun Zhang
标识
DOI:10.1016/j.brainresbull.2022.01.013
摘要
Hormone therapy (HT) has failed to improve learning and memory in postmenopausal women according to recent clinical studies; however, the reason for failure of HT in improving cognitive performance is unknown. In our research, we found cognitive flexibility was improved by 17β-Estradiol (E2) in mice 1 week after ovariectomy (OVXST), but not in mice 3 months after ovariectomy (OVXLT). Isobaric tags for relative and absolute quantitation (iTRAQ) revealed increased cannabinoid receptor interacting protein 1 (CNRIP1) in E2-treated OVXLT mice compared with E2-treated OVXST mice. Adeno-associated virus 2/9 (AAV2/9) delivery of Cnrip1 short-hairpin small interfering RNA (Cnrip1-shRNA) rescued the impaired cognitive flexibility in E2 treated OVXLT mice. This effect is dependent on CB1 function, which could be blocked by AM251-a CB1 antagonist. Our results indicated a new method to increasing cognitive flexibility in women receiving HT by disrupting CNRIP1.
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