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Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury
Author(s) -
Lepore Angelo C.,
O'donnell John,
Kim Andrew S.,
Yang Eun Ju,
Tuteja Alisha,
HaidetPhillips Amanda,
O'Banion Colin P.,
Maragakis Nicholas J.
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21241
Subject(s) - astrocyte , glutamate receptor , excitotoxicity , spinal cord injury , biology , spinal cord , neuroscience , glutamate aspartate transporter , central nervous system , glial scar , excitatory amino acid transporter , medicine , biochemistry , receptor
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. © 2011 Wiley‐Liss, Inc.