Department of Clinical Psychology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, 266035, China.
Qingdao No.9 High School, Shandong Province, Qingdao, Shandong, 266000, China.
Eur J Pharmacol. 2024 Nov 5;982:176939. doi: 10.1016/j.ejphar.2024.176939. Epub 2024 Aug 23.
The efficacy and tolerability of current antidepressants for adolescent depression are inadequate. S-adenosylmethionine (SAMe), known for its effectiveness and minimal side effects in adult depression, remains unstudied in adolescents. This study explored the potential of SAMe to address depression-like behaviors in juvenile rats induced by chronic unpredictable mild stress (CUMS), with a focus on gut microbiome interactions. Adolescent male Wistar rats were subjected to a 4-week CUMS regimen and received daily intraperitoneal injections of 300 mg/kg SAMe. Behavioral assessments included the sucrose preference test, elevated plus maze test, open field test, and Y-maze test. Histopathological changes of the hippocampus and colon were observed by Nissl staining and hematoxylin and eosin staining, respectively. Gut microbiome composition was analyzed using Accurate 16S absolute quantification sequencing. The results showed that SAMe significantly improved behavioral outcomes, reduced histopathological damages in hippocampal neurons and colon tissues, and modulated the gut microbiota of depressed rats. It favorably altered the ratio of Bacteroidetes to Firmicutes, decreased the absolute abundance of Deferribacteres, and adjusted levels of key microbial genera associated with depression-like behaviors. These results suggested that SAMe could effectively counter depression-like behaviors in CUMS-exposed adolescent rats by mitigating hippocampal neuronal and colon damage and modulating the gut microbiota. This supports SAMe as a viable and tolerable treatment option for adolescent depression, highlighting the importance of the gut-brain axis in therapeutic strategies.
当前用于治疗青少年抑郁症的抗抑郁药疗效和耐受性不足。S-腺苷甲硫氨酸（SAMe）在成人抑郁症中以疗效好和副作用小而闻名，但尚未在青少年中进行研究。本研究探讨了 SAMe 治疗慢性不可预测轻度应激（CUMS）诱导的青少年大鼠抑郁样行为的潜力，重点关注肠道微生物组的相互作用。将雄性 Wistar 青春期大鼠进行为期 4 周的 CUMS 处理，并每天接受 300mg/kg SAMe 的腹腔内注射。行为评估包括蔗糖偏好测试、高架十字迷宫测试、旷场测试和 Y 迷宫测试。通过尼氏染色和苏木精和伊红染色分别观察海马和结肠的组织病理学变化。使用 Accurate 16S 绝对定量测序分析肠道微生物组组成。结果表明，SAMe 显著改善了行为结果，减轻了海马神经元和结肠组织的组织病理学损伤，并调节了抑郁大鼠的肠道微生物群。它有利于改变拟杆菌门与厚壁菌门的比例，降低脱硫杆菌的绝对丰度，并调节与抑郁样行为相关的关键微生物属的水平。这些结果表明，SAMe 可通过减轻海马神经元和结肠损伤以及调节肠道微生物群有效对抗 CUMS 暴露的青少年大鼠的抑郁样行为。这支持 SAMe 作为青少年抑郁症的一种可行且耐受的治疗选择，强调了肠道-大脑轴在治疗策略中的重要性。
