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