Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport

Experimental Neurology
Charles R BuckRobert J McKeon

Abstract

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.

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Citations

Jun 12, 2003·Molecular and Cellular Neurosciences·Michael J JurynecCharles R Buck
Dec 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elizabeth N GendaMichael B Robinson
Jul 14, 2012·Journal of Toxicology and Environmental Health. Part a·Vanessa ValdiglesiasBlanca Laffon
Aug 7, 2013·Journal of Neuroimmunology·Sergey KalininDouglas L Feinstein
Aug 30, 2011·Biochimica Et Biophysica Acta·Pinar CoskunDouglas C Wallace
Mar 26, 2016·Neurochemistry International·Michael B Robinson, Joshua G Jackson
Jan 18, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Carolina SamuelssonElisabeth Ronne-Engström

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