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Inflammation, Glutamate, and Glia in Depression: A Literature Review

Published online by Cambridge University Press:  07 November 2014

Leah McNally ,
Zubin Bhagwagar  and
Jonas Hannestad
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Abstract

Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-α treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.

Type
Review Articles
Information
CNS Spectrums , Volume 13 , Issue 6 , June 2008 , pp. 501 - 510
Copyright
Copyright © Cambridge University Press 2008

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