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Biochem Biophys Res Commun. 2014 Jun 6;448(3):335-41. doi: 10.1016/j.bbrc.2014.04.017. Epub 2014 Apr 13.

Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes.

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Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
Department of Medicine, University of Montreal, Montreal, Quebec, Canada. Electronic address:


Loss of astrocytic glutamate transporters is a major feature of both thiamine deficiency (TD) and Wernicke's encephalopathy. However, the underlying basis of this process is not well understood. In the present study we have investigated the possibility of release of astrocytic soluble factors that might be involved in the regulation of the glutamate transporter GLT-1b in these cells. Treatment of naïve astrocytes with conditioned media from astrocytes exposed to TD conditions resulted in a progressive decrease in glutamate uptake over 24 h. Immunoblotting and flow cytometry measurements indicated this was accompanied by a 20-40% loss of GLT-1b. Astrocytes exposed to either TD or TD conditioned media showed increased disruption of mitochondrial membrane potential compared to control cells, and treatment of astrocytes with TD resulted in an increase in the pro-inflammatory cytokine TNF-α and elevated levels of phospho-IκB fragment, indicative of increased activation of NF-κB. Inhibition of TNF-α activity with the use of a neutralizing antibody blocked the increased NF-κB activation, while inhibition of NF-κB ameliorated the decrease in GLT-1b and reversed the decrease in glutamate uptake occurring with TD treatment. Together, these findings indicate that astrocytes exposed to TD conditions show responses suggesting that soluble factors released by these cells under conditions of TD play a regulatory role in terms of glutamate transport function and mitochondrial integrity.


Excitotoxicity; GLT-1; Mitochondrial membrane potential; NF-κB; Vitamin B1; Wernicke’s encephalopathy

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