Sex-specific effects of social isolation stress and ketamine on hippocampal plasticity.
Sex-specific effects of social isolation stress and ketamine on hippocampal plasticity.
复制标题
DOI：
10.1016/j.neulet.2021.136301
复制
发表时间：
2022-01-01
影响因子：
2.5
通讯作者：
Kabbaj M
中科院分区：
文献类型：
--
作者：
Logue J;Schoepfer K;Guerrero AB;Zhou Y;Kabbaj M
慢性社会隔离压力（SIS）会对大脑产生持久的负面影响，包括记忆缺陷，认知障碍和情绪改变，如抑郁和焦虑。所有这些症状，至少部分反映了海马功能的下降。在临床和临床前研究中，亚麻醉剂量的NMDA受体拮抗剂氯胺酮（KET）被证明具有快速和持久的抗抑郁作用。动物研究表明，生物性别和性腺激素水平改变了KET的行为效应，卵巢激素增加了对KET抗抑郁作用的敏感性。由于海马在介导SIS的一些作用中起关键作用，并且考虑到低剂量的KET已被证明可以挽救隔离饲养的一些行为缺陷，因此本研究旨在评估隔离应激对SIS中饲养的雄性和雌性大鼠突触前和突触后海马功能的影响，以及确定是否可以通过单次注射亚麻醉剂量的KET来挽救某些生理缺陷。为此，将断奶后的Sprague-Dawley大鼠在社会隔离或同性笼友中饲养5至7周。雄性和雌性大鼠在发情间期或发情前期接受单次注射KET（0，2.5，或5.0 mg/kg）3小时前终止和收集急性海马切片离体电生理场电位记录。长时程增强（LTP）和成对脉冲易化（PPF）输出在一个典型的CA 3-CA 1背海马电路进行了评估。我们的数据表明，SIS抑制海马LTP，而不影响PPF在雄性大鼠中，效果是由KET拯救。在雌性大鼠中，隔离应激并没有改变LTP，但确实降低了PPF -特别是当雌性大鼠在动情间期进行测试时-这种效果被最高剂量的KET所挽救。因此，我们的数据表明，性别差异的贡献前和突触后海马区室在应激和KET。
Chronic social isolation stress (SIS) induces lasting negative effects on the brain, including memory deficits, cognitive impairments, and mood alterations such as depression and anxiety. All these symptoms, at least in part, reflect reduced hippocampal function. In both clinical and preclinical studies, subanesthetic doses of the NMDA receptor antagonist, ketamine (KET), was shown to have rapid and lasting antidepressant effects. Animal studies have shown that biological sex and levels of gonadal hormones alter the behavioral effects of KET, with ovarian hormones increasing sensitivity to the antidepressant-like effects of KET. Since the hippocampus plays a key role in mediating some of the effects of SIS, and considering that KET at low doses has been shown to rescue some of the behavioral deficits of isolation rearing this study aimed to assess the effects of isolation stress on pre- and post-synaptic hippocampal functions in male and female rats reared in SIS, as well as determine whether some of the physiological deficits can be rescued with a single injection of sub-anesthetic doses of KET. To do this, Sprague-Dawley rats were raised from weaning in either social isolation or with same-sex cage mate for 5 to 7 weeks. Male and female rats in either diestrus of proestrus received a single injection of KET (0, 2.5, or 5.0 mg/kg) three hours prior to termination and collection of acute hippocampal slices for ex vivo electrophysiological field potential recordings. Long-term potentiation (LTP) and paired pulse facilitation (PPF) outputs were assessed in a canonical CA3-CA1 dorsal hippocampal circuit. Our data show that SIS inhibits hippocampal LTP without affecting PPF in male rats, an effect that was rescued by KET. In female rats, isolation stress did not alter LTP, but did reduce PPF - especially when females were tested in diestrus-, an effect that was rescued by KET at the highest dose. Our data thus suggest sex differences in the contribution of pre-and postsynaptic hippocampal compartments in response to stress and KET.
登录
查看更多内容
影响因子：
3.6
作者：
Aleksandrova, Lily R.;Wang, Yu Tian;Phillips, Anthony G.
通讯作者：
Phillips, Anthony G.
影响因子：
5.1
作者：
De Bellis MD;Woolley DP;Hooper SR
通讯作者：
Hooper SR
DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li N;Lee B;Liu RJ;Banasr M;Dwyer JM;Iwata M;Li XY;Aghajanian G;Duman RS
通讯作者：
Duman RS
影响因子：
2.7
作者：
Alshammari, Tahani K.;Alghamdi, Hajar;Alshammari, Musaad A.
通讯作者：
Alshammari, Musaad A.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH