title: Trehalose induced antidepressant-like effects and autophagy enhancement in mice.
abstract: BACKGROUND
  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.
authors: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
authors: N Z
authors: NZ
authors: Kara
authors: L
authors: L
authors: Toker
authors: G
authors: G
authors: Agam
authors: G W
authors: GW
authors: Anderson
authors: R H
authors: RH
authors: Belmaker
authors: H
authors: H
authors: Einat
mesh_terms: D000661:Amphetamine / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008320:Maltose / Q000008:administration & dosage; D051379:Mice; D008813:Mice, Inbred ICR; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D014199:Trehalose / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; C584111:Becn2 protein, mouse; D000697:Central Nervous System Stimulants; C490981:Gtf2h1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D013549:Sweetening Agents; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D008320:Maltose; D014199:Trehalose; D000661:Amphetamine
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