Trehalose induced antidepressant-like effects and autophagy enhancement in mice
Trehalose induced antidepressant-like effects and autophagy enhancement in mice
复制标题
DOI：
10.1007/s00213-013-3119-4
复制
发表时间：
2013-09-01
影响因子：
3.4
通讯作者：
Einat, H.
中科院分区：
文献类型：
--
作者：
Kara, N. Z.;Toker, L.;Einat, H.
基本原理 二糖海藻糖可保护细胞免受缺氧和缺氧损伤，并抑制蛋白质聚集。海藻糖的体内研究显示对神经退行性疾病动物模型的细胞和行为有益作用。此外，海藻糖被证明可以增强自噬，这一过程最近被认为与抗抑郁药和情绪稳定药物的治疗作用有关。 目的 因此，本研究旨在探讨海藻糖在抑郁症和躁狂动物模型中的抗抑郁和情绪稳定活性。 方法 将 1% 或 2% 海藻糖作为饮用溶液给予瑞士黑鼠（躁狂样行为模型），持续 3 周，或将 2% 海藻糖作为饮用溶液给予黑瑞士小鼠（躁狂样行为模型），持续 3 周。 ICR 小鼠及其行为在许多与抑郁或躁狂相关的测试中进行了评估。将海藻糖的效果与类似的长期施用二糖麦芽糖以及载体（水）对照进行比较。结果 长期施用海藻糖导致额叶皮层 p62/beclin-1 比率降低，表明自噬增强。海藻糖对瑞士黑小鼠的躁狂样行为没有稳定情绪的作用，但反而会增强安非他明引起的多动症，其作用类似于抗抑郁药物。在 ICR 小鼠中，海藻糖不会改变自发活动或安非他明引起的多动症，但在两个独立的实验中，在强迫游泳测试（抗抑郁样作用的标准筛选测试）中对减少不动有显着效果。结论结果表明海藻糖可能具有抗抑郁样特性。据推测，这些行为变化可能与海藻糖增强自噬的作用有关。
Rationale The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs.Objective The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania.Methods Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control.Results Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects.Conclusions The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.