[en] Thiamine 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)-3β. While decreased GSK-
3β activity appears to impair memory, increased GSK-3β activity is
associated with the distressed/depressed state. However, direct evidence
for the effects of thiamine on GSK-3β function were not have 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-3β activity and whether such administration impacts on
GSK-3β 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. Imipramine (7.5
mg/kg/day) was administered as a positive control for thiamine or
benfotiamine. As for imipramine, both compounds inhibited the
upregulation of GSK-3β 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. Together, our data indicate that
thiamine and benfotiamine have antidepressant/anti-stress effects in
naïve animals that are associated with reduced GSK-3β expression.
Importantly, the treatment also had pro-cognitive actions despite the
impact on GSK-3β activity.
Research center :
Giga-Neurosciences - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Markova, Nataliia ✱
Bazhenova, Nataliya ✱
Anthony, Daniel C
Vignisse, Julie
Svistunov, Andrey
Lesch, Klaus-Peter
Bettendorff, Lucien ✱; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Strekalova, Tatyana ✱
✱ These authors have contributed equally to this work.
Language :
English
Title :
Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stressinduced behaviours in mice
Publication date :
2017
Journal title :
Progress in Neuro-Psychopharmacology and Biological Psychiatry
ISSN :
0278-5846
eISSN :
1878-4216
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
75
Pages :
148-156
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] European Community
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