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Cannabidiol reverses memory impairments and activates components of the Akt/GSK3β pathway in an experimental model of estrogen depletion
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2021-08-24 , DOI: 10.1016/j.bbr.2021.113555
Márcio da Silveira Corrê 1 , Betânia Souza de Freitas 2 , Gustavo Dalto Barroso Machado 2 , Vivian Naziaseno Pires 2 , Elke Bromberg 3 , Jaime E C Hallak 4 , Antônio Waldo Zuardi 4 , José Alexandre S Crippa 4 , Nadja Schröder 5
Affiliation  

Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from , on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3β survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway’s activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD.

中文翻译:


在雌激素耗竭的实验模型中,大麻二酚可逆转记忆障碍并激活 Akt/GSK3β 通路的成分



临床和临床前证据表明,雌激素消耗会导致记忆障碍并增加神经损伤的易感性。在这里,我们试图研究大麻二酚(CBD)(一种来自 的非拟精神病化合物)对雌激素耗竭引起的大鼠记忆缺陷的影响及其潜在机制。成年大鼠接受双侧卵巢切除术(一种在啮齿类动物中建立的雌激素消耗模型)或假手术,并允许恢复三周。此后,他们每天注射 CBD(10mg/kg),持续十四天。老鼠接受了抑制性回避任务的测试,这是一种情绪驱动的记忆。行为测试后,他们被安乐死,并分离出他们的海马,用于分析 Akt/GSK3β 生存途径和抗凋亡蛋白 Bcl2 的成分。结果显示,卵巢切除术损害了回避记忆,而 CBD 能够完全逆转雌激素耗竭引起的记忆障碍。卵巢切除术还通过降低 Akt 和 GSK3β 的磷酸化水平以及 Bcl2 水平来减少 Akt/GSK3β 通路的激活,而 CBD 可以改善这种情况。
更新日期:2021-08-24
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