Loss of the glutamate transporter splice-variant GLT-1b in inferior colliculus and its prevention by ceftriaxone in thiamine deficiency.
Downregulation of astrocytic glutamate transporters is a feature of thiamine deficiency (TD), the underlying cause of Wernicke's encephalopathy, and plays a major role in its pathophysiology. Recent investigations suggest that ceftriaxone, a β-lactam antibiotic, stimulates GLT-1 expression and confers neuroprotection against ischemic and motor neuron degeneration. Thus, ceftriaxone treatment may be a protective strategy against excitotoxic conditions. In the present study, we examined the effects of ceftriaxone on the glutamate transporter splice-variant GLT-1b in rats with TD and in cultured astrocytes under TD conditions. Our results indicate that ceftriaxone protects against loss of GLT-1b levels in the inferior colliculus during TD, but with no significant effect in the thalamus and frontal cortex by immunoblotting and immunohistochemistry. Ceftriaxone also normalized the loss of GLT-1b in astrocyte cultures under conditions of TD. These results suggest that ceftriaxone has the ability to increase GLT-1b levels in astrocytes during TD, and may be an important pharmacological strategy for the treatment of excitotoxicity in this disorder.
Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
Shivraj S
SS
Jhala
Dongmei
D
Wang
Alan S
AS
Hazell
D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D027342:Excitatory Amino Acid Transporter 2 / Q000172:deficiency* / Q000235:genetics; D007245:Inferior Colliculi / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*
D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; D002443:Ceftriaxone