Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
Behav Brain Res. 2019 May 17;364:274-280. doi: 10.1016/j.bbr.2019.02.011. Epub 2019 Feb 6.
Depression is associated with dysregulation of methyl group metabolism such as low S-adenosylmethionine (SAM). We previously reported that Flinders Sensitive Line (FSL) rats, an animal model of depression, had lower concentrations of liver SAM than the control rats, Flinders Resistant Line (FRL) rats. The present study investigated if SAM supplementation may correct liver SAM and behavioral abnormalities in this model. Moreover, we compared one-carbon (C1) metabolites, neurotransmitters, and gastrointestinal (GI) transit in SAM-treated versus imipramine (IMI)-treated animals. FSL rats received vehicle, IMI, SAM, or IMI + SAM (n = 9-10 per group) once daily through oral gavage for 4 weeks; FRL rats received vehicle. Behavior was assessed using standard tests for locomotion, cognition, and depressive-like behavior. Monoamine neurotransmitters and C1 metabolites were measured using UHPLC-ECD and UPLC-MS/MS, respectively. Compared to FRL rats, FSLs had lower liver SAM, higher plasma serotonin, lower hippocampal dopamine and serotonin turnover, and faster GI transit. Behaviorally, FSL rats showed impaired cognitive performance as well as increased depressive-like behavior compared to FRLs. Coadministration of IMI and SAM seemed to have adverse effects on spatial memory. SAM or IMI administration did not reverse C1 metabolites, neurotransmitters, or GI transit in FSLs. Despite low liver SAM in FSL rats, orally administered SAM did not show antidepressant effects in this specific animal model of depression.
抑郁与甲基化代谢物的调节异常有关，如 S-腺苷甲硫氨酸（SAM）水平降低。我们之前报道过，抑郁动物模型弗林德斯敏感型（FSL）大鼠的肝脏 SAM 浓度低于对照的弗林德斯抵抗型（FRL）大鼠。本研究旨在探讨 SAM 补充是否可以纠正该模型的肝脏 SAM 和行为异常。此外，我们比较了 SAM 治疗组和丙咪嗪（IMI）治疗组的单碳（C1）代谢物、神经递质和胃肠道（GI）转运情况。FSL 大鼠每天通过口服灌胃接受 vehicle、IMI、SAM 或 IMI+SAM（每组 n=9-10）治疗 4 周；FRL 大鼠接受 vehicle。使用标准的运动、认知和抑郁样行为测试评估行为。单胺神经递质和 C1 代谢物分别采用 UHPLC-ECD 和 UPLC-MS/MS 进行测量。与 FRL 大鼠相比，FSL 大鼠的肝脏 SAM 水平较低，血浆 5-羟色胺水平较高，海马多巴胺和 5-羟色胺周转率较低，GI 转运较快。行为上，与 FRL 大鼠相比，FSL 大鼠的认知表现受损，且抑郁样行为增加。IMI 和 SAM 的联合给药似乎对空间记忆有不良影响。SAM 或 IMI 给药并未逆转 FSL 大鼠的 C1 代谢物、神经递质或 GI 转运。尽管 FSL 大鼠的肝脏 SAM 水平较低，但口服 SAM 并未在该特定的抑郁动物模型中显示出抗抑郁作用。
