Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport.

Buck CR, Jurynec MJ, Gupta DK, Law AK, Bilger J, Wallace DC, McKeon RJ
Exp Neurol. 2003 181 (2): 149-58

PMID: 12781988 · PMCID: PMC2821056 · DOI:10.1016/s0014-4886(03)00043-8

A hallmark of central nervous system (CNS) pathology is reactive astrocyte production of the chronic glial scar that is inhibitory to neuronal regeneration. The reactive astrocyte response is complex; these cells also produce neurotrophic factors and are responsible for removal of extracellular glutamate, the excitatory neurotransmitter that rises to neurotoxic levels in injury and disease. To identify genes expressed by reactive astrocytes, we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Ant1, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria. Ant1 expression in reactive astrocytes is regulated by transforming growth factor-beta1, a pluripotent CNS injury-induced cytokine. The significance of increased Ant1 is evident from the observation that glutamate uptake is significantly decreased in astrocytes from Ant1 null mutant mice while a specific Ant inhibitor reduces glutamate uptake in wild-type astrocytes. Thus, the astrocytic response to CNS injury includes an apparent increase in energy mobilization capacity by Ant1 that contributes to neuroprotective, energy-dependent glutamate uptake.

MeSH Terms (23)

Adenine Nucleotide Translocator 1 Animals Astrocytes Atractyloside Biological Transport Brain Injuries Cells, Cultured Collodion Disease Models, Animal Gene Expression Profiling Gene Expression Regulation Genes, Reporter Gliosis Glutamic Acid Implants, Experimental Male Mice Mitochondria Polymerase Chain Reaction Rats RNA, Messenger Transforming Growth Factor beta Transforming Growth Factor beta1

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