Astrocytes are a major target in thiamine deficiency and Wernicke's encephalopathy.
Thiamine deficiency (TD) is the underlying cause, and an established model, of Wernicke's encephalopathy (WE). Although the neurologic dysfunction and brain damage that results from TD has been well-described, the precise mechanisms that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various processes have been proposed that could lead to focal neuronal cell death in this disorder. But despite a concerted effort to relate these processes to a clear sequelae of events culminating in development of the focal neuropathology, little success has resulted. In recent years, however, a role for astrocytes in the pathophysiology of TD has been emerging. Here, alterations in glutamate uptake, and levels of the astrocytic glutamate transporters EAAT1 and EAAT2 in TD and WE, are discussed in terms of an excitotoxic event, along with the GABA transporter subtype GAT-3, and changes in other astrocytic proteins including GFAP and glutamine synthetase. Lactic acidosis, changes in the water channel protein AQP-4 and brain edema are also a focus of attention in relation to astrocyte dysfunction, while involvement of oxidative stress and inflammatory processes, along with white matter injury in terms of excitotoxicity are other key issues considered. In summary, a new appraisal of the extent of involvement of astrocytes in TD and WE is presented, with the evidence suggesting these cells represent a major target for damage during the disease process.
Department of Medicine, University of Montreal, Montreal, Quebec, Canada. alan.stewart.hazell@umontreal.ca
Alan S
AS
Hazell
D000140:Acidosis, Lactic / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D013832:Thiamine Deficiency / Q000473:pathology*; D014882:Water-Electrolyte Balance / Q000502:physiology; D014899:Wernicke Encephalopathy / Q000473:pathology*