title: Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury.
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.
authors: Department of Neuroscience, Thomas Jefferson University Medical College, 900 Walnut St., Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors: Angelo C
authors: AC
authors: Lepore
authors: John
authors: J
authors: O'Donnell
authors: Andrew S
authors: AS
authors: Kim
authors: Eun Ju
authors: EJ
authors: Yang
authors: Alisha
authors: A
authors: Tuteja
authors: Amanda
authors: A
authors: Haidet-Phillips
authors: Colin P
authors: CP
authors: O'Banion
authors: Nicholas J
authors: NJ
authors: Maragakis
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000172:deficiency / Q000235:genetics*; D005911:Gliosis / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C493396:Slc1a2 protein, mouse; D018698:Glutamic Acid