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Mol Cell Neurosci. 2017 Jul;82:126-136. doi: 10.1016/j.mcn.2017.05.005. Epub 2017 May 12.

Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

Author information

1
GIGA-Neurosciences, University of Liege, Liege, Belgium.
2
Laboratory of Psychiatric Neurobiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
3
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Moscow, Russia.
4
Department of Pharmacology, Oxford University, Oxford, UK.
5
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Moscow, Russia; Department of Pharmacology, Oxford University, Oxford, UK; Institute of General Pathology and Pathophysiology, Moscow 125 315, Russia; Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
6
Laboratory of Psychiatric Neurobiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Institute of General Pathology and Pathophysiology, Moscow 125 315, Russia; Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
7
Laboratory of Psychiatric Neurobiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands. Electronic address: t.strekalova@maastrichtuniversity.nl.
8
GIGA-Neurosciences, University of Liege, Liege, Belgium. Electronic address: L.Bettendorff@ulg.ac.be.

Abstract

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 (200mg/kg/day in drinking water for 20days) 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.

KEYWORDS:

Thiamine; benfotiamine; hippocampus; neurogenesis; oxidative stress; predator stress; survival

PMID:
28506637
DOI:
10.1016/j.mcn.2017.05.005
[Indexed for MEDLINE]

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