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Microglial self-defence mediated through GLT-1 and glutathione

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Abstract

Glutamate is stored in synaptic vesicles in presynaptic neurons. It is released into the synaptic cleft to provide signalling to postsynaptic neurons. Normally, the astroglial glutamate transporters GLT-1 and GLAST take up glutamate to mediate a high signal-to-noise ratio in the synaptic signalling, and also to prevent excitotoxic effects by glutamate. In astrocytes, glutamate is transformed into glutamine, which is safely transported back to neurons. However, in pathological conditions, such as an ischemia or virus infection, astroglial transporters are down-regulated which could lead to excitotoxicity. Lately, it was shown that even microglia can express glutamate transporters during pathological events. Microglia have two systems for glutamate transport: GLT-1 for transport into the cells and the x −c system for transport out of the cells. We here review results from our work and others, which demonstrate that microglia in culture express GLT-1, but not GLAST, and transport glutamate from the extracellular space. We also show that TNF-α can induce increased microglial GLT-1 expression, possibly associating the expression with inflammatory systems. Furthermore, glutamate taken up through GLT-1 may be used for direct incorporation into glutathione and to fuel the intracellular glutamate pool to allow cystine uptake through the x −c system. This can lead to a defence against oxidative stress and have an antiviral function.

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Acknowledgments

The work performed in the authors’ laboratory was supported by the Swedish Research Council, LUA/ALF from the Sahlgrenska University Hospital and Edit Jacobson’s Foundation. The article is a summary of the thesis of Mikael Persson.

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  1. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, 1tr, 41345, Gothenburg, Sweden

    Mikael Persson & Lars Rönnbäck

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  1. Mikael Persson
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  2. Lars Rönnbäck
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Correspondence to Lars Rönnbäck.

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Persson, M., Rönnbäck, L. Microglial self-defence mediated through GLT-1 and glutathione. Amino Acids 42, 207–219 (2012). https://doi.org/10.1007/s00726-011-0865-7

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  • DOI: https://doi.org/10.1007/s00726-011-0865-7

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