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Thiamine Deficiency: An Update of Pathophysiologic Mechanisms and Future Therapeutic Considerations

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Abstract

Thiamine is an essential vitamin that is necessary to maintain the functional integrity of cells in the brain. Its deficiency is the underlying cause of Wernicke’s encephalopathy (WE), a disorder primarily associated with, but not limited to, chronic alcoholism. Thiamine deficiency leads to the development of impaired energy metabolism due to mitochondrial dysfunction in focal regions of the brain resulting in cerebral vulnerability. The consequences of this include oxidative stress, excitotoxicity, inflammatory responses, decreased neurogenesis, blood–brain barrier disruption, lactic acidosis and a reduction in astrocyte functional integrity involving a loss of glutamate transporters and other astrocyte-specific proteins which together contribute in a major way to the resulting neurodegeneration. Exactly how these factors acting in concert lead to the demise of neurons is unclear. In this review we reassess their relative importance in the light of more recent findings and discuss therapeutic possibilities that may provide hope for the future for individuals with WE.

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Abbreviations

AD:

Alzheimer’s disease

ATN:

Anterior thalamic nuclei

BBB:

Blood–brain barrier

CNS:

Central nervous system

ER:

Endoplasmic reticulum

HD:

Huntington’s disease

α-KGDH:

Alpha-ketoglutarate dehydrogenase

IL-1β:

Interleukin-1 beta

NO:

Nitric oxide

NOS:

NO synthase

NSCs:

Neural stem cells

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SGZ:

Subgranular zone

O2 − :

Superoxide anion

SVZ:

Subventricular zone

TCA:

Tricarboxylic acid cycle

TD:

Thiamine deficiency

TNF-α:

Tumor necrosis factor-alpha

WE:

Wernicke’s encephalopathy

WKS:

Wernicke–Korsakoff syndrome

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Acknowledgments

The senior author (A.S.H.) is supported by the Canadian Institutes of Health Research (CIHR).

Author information

Authors and Affiliations

  1. Department of Medicine, University of Montreal, Montreal, QC, Canada

    Eman Abdou & Alan S. Hazell

  2. NeuroRescue Laboratory, CRCHUM, Tour Viger R09-432, 900 Saint-Denis, Montreal, QC, H2X 0A9, Canada

    Alan S. Hazell

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  1. Eman Abdou
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  2. Alan S. Hazell
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Correspondence to Alan S. Hazell.

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Special Issue: In honor of Michael Norenberg.

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Abdou, E., Hazell, A.S. Thiamine Deficiency: An Update of Pathophysiologic Mechanisms and Future Therapeutic Considerations. Neurochem Res 40, 353–361 (2015). https://doi.org/10.1007/s11064-014-1430-z

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  • DOI: https://doi.org/10.1007/s11064-014-1430-z

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