Loss of the glutamate transporter splice-variant GLT-1b in inferior colliculus and its prevention by ceftriaxone in thiamine deficiency

Neurochem Int. 2011 Apr;58(5):558-63. doi: 10.1016/j.neuint.2011.01.014. Epub 2011 Jan 20.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceftriaxone / pharmacology
  • Ceftriaxone / therapeutic use*
  • Cells, Cultured
  • Excitatory Amino Acid Transporter 2 / deficiency*
  • Excitatory Amino Acid Transporter 2 / genetics
  • Inferior Colliculi / drug effects
  • Inferior Colliculi / metabolism*
  • Male
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Thiamine Deficiency / genetics
  • Thiamine Deficiency / metabolism*
  • Thiamine Deficiency / prevention & control*

Substances

  • Excitatory Amino Acid Transporter 2
  • Protein Isoforms
  • Ceftriaxone