The role of 5-HT7R in the memory impairment of mice induced by long-term isoflurane anesthesia
The role of 5-HT7R in the memory impairment of mice induced by long-term isoflurane anesthesia
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5-HT7R在长期异氟烷麻醉所致小鼠记忆障碍中的作用
DOI：
10.1016/j.nlm.2022.107584
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发表时间：
2022-01
影响因子：
2.7
通讯作者：
Xiaoping Gu
中科院分区：
文献类型：
--
作者：
Tiantian Liu;Jia Song;Qingyun Zhou;Shuaishuai Chu;Yujia Liu;Xin Zhao;Zhengliang Ma;Tianjiao Xia;Xiaoping Gu
全身麻醉广泛应用于临床手术和诊断过程。然而，越来越多的证据表明，麻醉剂暴露可能会对认知功能产生负面影响。不幸的是，人们对麻醉引起的认知功能障碍的潜在机制和有效的预防和治疗策略知之甚少。 5-HT7R 是一种血清素受体家族成员，在功能上与学习和记忆相关。由于其配体具有广泛的神经药理作用，它最近已成为各种神经系统疾病的潜在治疗靶点。然而，5-HT7R 在长期异氟烷麻醉引起的记忆障碍中的作用以及麻醉前预先激活或阻断 5-HT7R 是否对这种记忆障碍具有调节作用仍不清楚。本研究在麻醉前对小鼠腹腔注射5-HT7R选择性激动剂LP-211和5-HT7R选择性拮抗剂SB-269970；使用恐惧条件反射测试和新物体识别测试评估它们对小鼠认知表现的影响。此外，利用qRT-PCR检测海马中5-HT7R的转录水平，并通过蛋白质组学探讨其潜在机制。因此，长期暴露于异氟烷麻醉会导致记忆障碍和海马 5-HT7R mRNA 表达增加，SB-269970 预处理可以减弱这种影响，但 LP-211 预处理则不能。根据蛋白质组学结果，SB-269970预处理的抗遗忘作用可能归因于其对Slc6a11、Itpka、Arf3、Srcin1和Epb41l2基因表达以及海马突触组织的作用。总之，5-HT7R 参与了长期异氟烷麻醉引起的记忆损伤，并且用 SB-269970 预先阻断 5-HT7R 可保护记忆损伤。这一发现可能有助于提高对长期异氟烷麻醉引起的记忆障碍的理解，并针对长期异氟烷暴露后的不良反应构建潜在的预防和治疗策略。
General anesthesia is widely utilized in the clinic for surgical and diagnostic procedures. However, growing evidence suggests that anesthetic exposure may affect cognitive function negatively. Unfortunately, little is known about the underlying mechanisms and efficient prevention and therapeutic strategies for the anesthesia-induced cognitive dysfunction. 5-HT7R, a serotonin receptor family member, is functionally associated with learning and memory. It has recently become a potential therapeutic target in various neurological diseases as its ligands have a wide range of neuropharmacological effects. However, it remains unknown the role of 5-HT7R in the long-term isoflurane anesthesia-induced memory impairment and whether prior activation or blockade of 5-HT7R before anesthesia has modulating effects on this memory impairment. In this study, 5-HT7R selective agonist LP-211 and 5-HT7R selective antagonist SB-269970 were pretreated intraperitoneally to mice before anesthesia; their effects on the cognitive performance of mice were assessed using fear conditioning test and novel object recognition test. Furthermore, the transcriptional level of 5-HT7R in the hippocampus was detected using qRT-PCR, and proteomics was conducted to probe the underlying mechanisms. As a result, long-term exposure to isoflurane anesthesia caused memory impairment and an increase in hippocampal 5-HT7R mRNA expression, which could be attenuated by SB-269970 pretreatment but not LP-211pretreatment. According to the proteomics results, the antiamnestic effect of SB-269970 pretreatment was probably attributed to its action on the gene expression of Slc6a11, Itpka, Arf3, Srcin1, and Epb41l2, and synapse organization in the hippocampus. In conclusion, 5-HT7R is involved in the memory impairment induced by long-term isoflurane anesthesia, and the prior blockade of 5-HT7R with SB-269970 protects the memory impairment. This finding may help to improve the understanding of the long-term isoflurane anesthesia-induced memory impairment and to construct potential preventive and therapeutic strategies for the adverse effects after long-term isoflurane exposure.
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影响因子：
5.7
作者：
Zhang B;Tian M;Zhen Y;Yue Y;Sherman J;Zheng H;Li S;Tanzi RE;Marcantonio ER;Xie Z
通讯作者：
Xie Z
影响因子：
13.5
作者：
Leopoldo, Marcello;Lacivita, Enza;Berardi, Francesco;Perrone, Roberto;Hedlund, Peter B.
通讯作者：
Hedlund, Peter B.
影响因子：
1.7
作者：
Jiang, Shan;Miao, Bei;Chen, Ying
通讯作者：
Chen, Ying
影响因子：
2.7
作者：
Gasbarri, Antonella;Cifariello, Agata;Meneses, Alfredo
通讯作者：
Meneses, Alfredo
DOI：
10.1016/s0021-9258(19)49479-9
发表时间：
1993-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Bard;J. Zgombick;N. Adham;P. Vaysse;T. Branchek;R. Weinshank
通讯作者：
J. Bard;J. Zgombick;N. Adham;P. Vaysse;T. Branchek;R. Weinshank