Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury
- 31 August 2011
- Vol. 59 (12), 1996-2005
- https://doi.org/10.1002/glia.21241
Abstract
The astrocyte glutamate transporter, GLT1, is responsible for the vast majority of glutamate uptake in the adult central nervous system (CNS), thereby regulating extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate dysregulation plays a central role in outcome following traumatic spinal cord injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI, mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/−) and wild‐type mice received thoracic crush SCI. Compared with wild‐type controls, GLT1+/− mice had an attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing. GLT1+/− mice showed a decrease in intraspinal GLT1 protein and functional glutamate uptake compared with wild‐type mice, accompanied by increased apoptosis and neuronal loss following crush injury. These results suggest that astrocyte GLT1 plays a role in limiting secondary cell death following SCI, and also show that compromise of key astrocyte functions has significant effects on outcome following traumatic CNS injury. These findings also suggest that increasing intraspinal GLT1 expression may represent a therapeutically relevant target for SCI treatment.Keywords
This publication has 36 references indexed in Scilit:
- Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1G93A miceExperimental Neurology, 2006
- Basso Mouse Scale for Locomotion Detects Differences in Recovery after Spinal Cord Injury in Five Common Mouse StrainsJournal of Neurotrauma, 2006
- Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injuryNeurochemistry International, 2006
- Pharmacological Approaches To Repair the Injured Spinal CordJournal of Neurotrauma, 2006
- Spinal Cord InjuryAmerican Journal of Physical Medicine & Rehabilitation, 2003
- Functional Changes of Glial Glutamate Transporter GLT-1 during Ischemia: An In Vivo Study in the Hippocampal CA1 of Normal Mice and Mutant Mice Lacking GLT-1Journal of Neuroscience, 2003
- Transplantation of neural stem cells into the spinal cord after injurySeminars in Cell & Developmental Biology, 2003
- NBQX Treatment Improves Mitochondrial Function and Reduces Oxidative Events after Spinal Cord InjuryJournal of Neurotrauma, 2002
- Rapid changes in expression of glutamate transporters after spinal cord injuryBrain Research, 2002
- Evidence that reversed glutamate uptake contributes significantly to glutamate release following experimental injury to the rat spinal cordBrain Research, 2000