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Role of Astrocytes in Delayed Neuronal Death: GLT-1 and its Novel Regulation by MicroRNAs

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Book cover Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 11))

Abstract

Astrocytes have been shown to protect neurons from delayed neuronal death and increase their survival in cerebral ischemia. One of the main mechanisms of astrocyte protection is rapid removal of excess glutamate from synaptic sites by astrocytic plasma membrane glutamate transporters such as GLT-1/EAAT-2, reducing excitotoxicity. Astrocytic mitochondrial function is essential for normal GLT-1 function. Manipulating astrocytic mitochondrial and GLT-1 function is thus an important strategy to enhance neuronal survival and improve outcome following cerebral ischemia. Increasing evidence supports the involvement of microRNAs (miRNA), some of them being astrocyte-enriched, in the regulation of cerebral ischemia. This chapter will first update the information about astrocytes, GLT-1, astrocytic mitochondria, and delayed neuronal death. Then we will focus on two recently reported astrocyte-enriched miRNAs (miR-181 and miR-29 families), their effects on astrocytic mitochondria and GLT-1 as well as on outcome after cerebral ischemia.

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Acknowledgments

Grant sponsor: NIH; Grant numbers: NS084396, NS053898, NS080177. The authors thank William Magruder for help preparing the manuscript.

Conflict of interest The authors have no conflicting financial interests.

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  1. Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, S272A and S290, Stanford, CA, 94305-5117, USA

    Yi-Bing Ouyang Ph.D., Lijun Xu M.D., Siwei Liu B.S., B.A. & Rona G. Giffard M.D., Ph.D.

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  1. Yi-Bing Ouyang Ph.D.
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  2. Lijun Xu M.D.
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Correspondence to Yi-Bing Ouyang Ph.D. or Rona G. Giffard M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Neurobiology CIRC 429, University of Alabama, Birmingham, Alabama, USA

    Vladimir Parpura

  2. Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

  3. Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom

    Alexei Verkhratsky

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Ouyang, YB., Xu, L., Liu, S., Giffard, R.G. (2014). Role of Astrocytes in Delayed Neuronal Death: GLT-1 and its Novel Regulation by MicroRNAs. In: Parpura, V., Schousboe, A., Verkhratsky, A. (eds) Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain. Advances in Neurobiology, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-08894-5_9

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