Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels
[en] Thiamine is essential for normal brain function and its deficiency causes metabolic
impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis
(AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert
neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of
neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed
C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation
(number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn
immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number
of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This
reduction was prevented when the mice were treated (200 mg/kg/day in drinking water for 20
days) with thiamine or benfotiamine, that were recently found to prevent stress-induced
behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS.
Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight
loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest
increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP)
remained unchanged, suggesting that the beneficial effects observed are not linked to the role
of this coenzyme in energy metabolism. Predator stress increased hippocampal protein
carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine
and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in
particular benfotiamine protects against paraquat-induced oxidative stress. We therefore
hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a
mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that
thiamine and benfotiamine prevent stress-induced inhibition of hippocampal neurogenesis and
accompanying physiological changes. The present data suggest that thiamine precursors with
high bioavailability might be useful as a complementary therapy in several neuropsychiatric
disorders.
Research Center/Unit :
Giga-Neurosciences - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vignisse, Julie ; Université de Liège > Département des maladies infectieuses et parasitaires (DMI) > Mycologie vétérinaire
Sambon, Margaux ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels
Publication date :
2017
Journal title :
Molecular and Cellular Neuroscience
ISSN :
1044-7431
eISSN :
1095-9327
Publisher :
Elsevier
Volume :
82
Pages :
126-136
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 602805 - AGGRESSOTYPE - Aggression subtyping for improved insight and treatment innovation in psychiatric disorders FP7 - 602805 - AGGRESSOTYPE - Aggression subtyping for improved insight and treatment innovation in psychiatric disorders
Name of the research project :
“5-100” Russian Research Excellence program
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture Fondation Recherche Alzheimer EU - European Union CE - Commission Européenne
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