Changes in glutamate transporter expression in mouse forebrain areas following focal ischemia.

Dysfunction of glutamate transporters has been proposed to promote neuronal death in modelled cerebral ischemia. However, these studies have produced conflicting results and the changes in glutamate transporter expression have not yet been examined in a mouse focal ischemic stroke model. This study used quantitative real-time reverse-transcription polymerase chain reaction to examine glutamate transporter mRNA expression in the hippocampus, cortex and striatum in a mouse model of focal ischemic stroke induced by middle cerebral artery occlusion (MCAO). Effects on mRNA expression of glial (GLT-1, GLAST) and neuronal (EAAC1) glutamate transporters in these brain areas were assessed by comparing MCAO brains with sham-operated control brains. Changes in transporter proteins were also assessed by immunohistochemistry using specific antibodies to GLT-1 and GLAST. Following focal ischemia, GLT-1 mRNA expression was decreased significantly in the ipsilateral hippocampus and cortex compared to the sham-operated brains (p<0.05). There were no significant differences in GLAST or EAAC1 mRNA expression between MCAO and sham-operated brains. Immunohistochemistry also confirmed a marked reduction in GLT-1 immunoreactivity in the cortex and hippocampus. Down regulation of GLT-1 in these brain areas may impair normal clearance of synaptically-released glutamate and contribute to neural damage following focal ischemic insult.

Ketheeswaranathan P ，Turner NA ，Spary EJ ，Batten TF ，McColl BW ，Saha S ... -  《-》

Expression of glutamate transporters GLT-1 and GLAST in different regions of rat brain during the course of experimental autoimmune encephalomyelitis.

Mitosek-Szewczyk K ，Sulkowski G ，Stelmasiak Z ，Struzyńska L ... -  《NEUROSCIENCE》

Changes in expression of neuronal and glial glutamate transporters in lead-exposed adult rat brain.

Struzyńska L ，Chalimoniuk M ，Sulkowski G 《NEUROCHEMISTRY INTERNATIONAL》

Early loss of the glutamate transporter splice-variant GLT-1v in rat cerebral cortex following lateral fluid-percussion injury.

Glutamate transporter proteins are essential for the control of interstitial glutamate levels, with an impairment of their function or levels being a major potential contributor to excitotoxicity. We have investigated the effects of lateral fluid percussion on the levels of the glutamate transporter proteins GLT-1alpha, its splice variant GLT-1v, GLAST, and EAAC1 in the rat in order to evaluate their pathogenetic role in this model of traumatic brain injury (TBI). Immunoblot analysis revealed neuronal loss in the cerebral cortex was accompanied by a 54% decrease in GLT-1v 6 h following the insult which progressed to an 83% loss of the transporter after 24 h. No changes in GLT-1alpha, GLAST, or EAAC1 were observed in this brain region at either time point. GLT-1v content was also decreased by 55% and 68% in the hippocampus and thalamus, respectively, at 6 h post-injury, but recovered fully after 24 h in both brain regions. In contrast, levels of GLT-1alpha were increased in the hippocampus at 6 h and 24 h post-TBI. These alterations in transporter protein content were also confirmed using immunohistochemical methods. Our results show for the first time a pattern of early, dynamic changes in the levels of GLT-1 transporter splice variants in different brain regions in this trauma model. In addition, correlation of GLT-1v levels with both neuronal cell loss and alpha-internexin content in the injured cortex suggests that loss of this novel glutamate transporter may be a key factor in determining cerebral vulnerability following this type of brain injury.

Yi JH ，Pow DV ，Hazell AS 《GLIA》

Region- and age-specific changes in glutamate transport in the AβPP23 mouse model for Alzheimer's disease.

Schallier A ，Smolders I ，Van Dam D ，Loyens E ，De Deyn PP ，Michotte A ，Michotte Y ，Massie A ... -  《-》