Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stress-induced behaviours in mice

Nataliia Markova, Nataliia Bazhenova, Daniel C. Anthony*, Julie Vignisse, Andrey Svistunov, Klaus-Peter Lesch, Lucien Bettendorff, Tatyana Strekalova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Thiamine (vitamin B1) deficiency in the brain has been implicated in the development of dementia and symptoms of depression. Indirect evidence suggests that thiamine may contribute to these pathologies by controlling the activities of glycogen synthase kinase (GSK)-3 beta. While decreased GSK-3 beta activity appears to impair memory, increased GSK-3 beta activity is associated with the distressed/depressed state. However, hitherto direct evidence for the effects of thiamine on GSK-3 beta function has not been reported. Here, we administered thiamine or, the more bioavailable precursor, benfotiamine at 200 mg/kg/day for 2 weeks to C57BL/6J mice, to determine whether treatment might affect behaviours that are known to be sensitive to GSK-3 beta activity and whether such administration impacts on GSK-3 beta expression within the brain. The mice were tested in models of contextual conditioning and extinction, a 5-day rat exposure stress test, and a modified swim test with repeated testing. The tricyclic antidepressant imipraMine (7.5 mg/kg/day), was administered as a positive control for the effects of thiamine or benfotiamine. As for imipramine, both compounds inhibited the upregulation of GSK-3 beta induced by predator stress or repeated swimming, and reduced floating scores and the predator stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine and benfotiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Our data indicate that thiamine and benfotiamine have antidepressant/anti-stress effects in naive animals that are associated With reduced GSK-3 beta expression and conditioning of adverse memories. Thus thiamine and benfotiamine may modulate GSK-3 beta functions in a manner that is dependent on whether the contextual conditioning is adaptive or maladaptive. (C) 2016 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalProgress in Neuro-Psychopharmacology & Biological Psychiatry
Publication statusPublished - 3 Apr 2017


  • Thiamine
  • Benfotiamine
  • Glycogene-synthase-ldnase-3-beta (GSK-3 beta)
  • Depression
  • Plasticity
  • Animal models
  • RATS
  • GSK-3-BETA

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