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海藻糖诱导小鼠产生抗抑郁样作用和自噬增强。

Trehalose induced antidepressant-like effects and autophagy enhancement in mice.

机构信息

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.

出版信息

Psychopharmacology (Berl). 2013 Sep;229(2):367-75. doi: 10.1007/s00213-013-3119-4. Epub 2013 May 5.

DOI:10.1007/s00213-013-3119-4
PMID:23644913
Abstract

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.

摘要

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。海藻糖的体内研究表明,在神经退行性疾病的动物模型中,它具有细胞和行为有益的作用。此外,海藻糖被证明可以增强自噬,最近有研究表明,自噬过程可能与抗抑郁药和情绪稳定剂的治疗作用有关。

目的

因此,本研究旨在探索海藻糖在抑郁和躁狂动物模型中的抗抑郁和情绪稳定作用。

方法

将海藻糖 1%或 2%作为饮用溶液连续 3 周给黑瑞士小鼠(躁狂样行为模型)或 2%给 ICR 小鼠,并在一系列与抑郁或躁狂相关的测试中评估其行为。将海藻糖的作用与类似的二糖麦芽糖的慢性给药以及与载体(水)对照进行比较。

结果

海藻糖的慢性给药导致前额皮质 p62/beclin-1 比值降低,提示自噬增强。海藻糖对黑瑞士小鼠的躁狂样行为没有稳定情绪的作用,但会增强安非他命引起的过度活跃,这一作用类似于抗抑郁药。在 ICR 小鼠中,海藻糖不改变自发活动或安非他命引起的过度活跃,但在两项独立的实验中,有显著作用可减少强迫游泳试验中的不动时间,这是一种抗抑郁样作用的标准筛选试验。

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。

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