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催产素治疗可改善地塞米松诱导的雌性小鼠抑郁样症状,其机制与增强海马 CREB-BDNF 信号有关。

Oxytocin treatment improves dexamethasone-induced depression-like symptoms associated with enhancement of hippocampal CREB-BDNF signaling in female mice.

机构信息

Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.

Division of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.

出版信息

Neuropsychopharmacol Rep. 2022 Sep;42(3):356-361. doi: 10.1002/npr2.12271. Epub 2022 Jun 21.

Abstract

AIMS

Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant-like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant-like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)-induced depression.

METHODS

Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety- and depression-like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants.

RESULTS

Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p-CREB and BDNF in the hippocampus.

CONCLUSION

OT may exert antidepressant-like effects by activating hippocampal CREB-BDNF signaling in a female mouse model of depression.

摘要

目的

慢性应激和糖皮质激素暴露是抑郁的危险因素。催产素 (OT) 已被证明对雄性啮齿动物具有抗应激和抗抑郁样作用。然而,女性患抑郁症的比例是男性的两倍,目前尚不清楚 OT 是否对患有抑郁症的女性具有抗抑郁样作用。因此,在这项研究中,我们研究了慢性 OT 给药在地塞米松 (DEX) 诱导的雌性小鼠抑郁模型中的治疗效果。

方法

雌性 C57BL/6J 小鼠每天接受生理盐水(载体,皮下注射)、DEX(皮下注射)或 OT(腹腔注射)+DEX(皮下注射)治疗 8 周,然后评估焦虑和抑郁样行为。我们还检查了海马体中磷酸化 cAMP 反应元件结合蛋白 (p-CREB) 和脑源性神经营养因子 (BDNF) 的水平,这是对抗抑郁药反应的重要介质。

结果

同时给予 OT 治疗可阻断 DEX 对情绪行为的不利影响。此外,它还上调了海马体中的 p-CREB 和 BDNF。

结论

OT 可能通过激活抑郁模型中小鼠海马体中的 CREB-BDNF 信号通路发挥抗抑郁样作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c9/9515699/5cfae497440b/NPR2-42-356-g002.jpg

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