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Author Notes:

Correspondence: L. Capuron, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro), INRA UMR 1286, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, Bordeaux, F-33076, France; Telephone: (+33) 5 57-57-12-33; Fax: (+33) 5 57-57-12-27; Email: lucile.capuron@bordeaux.inra.fr.

or A.H. Miller, Department of Psychiatry, Emory University School of Medicine, 1365-B Clifton Rd, Suite B5100, Room B5101, Atlanta, GA 30322; Telephone: 404-727-8260; Fax: 404-778-3965; Email: amill02@emory.edu.

Disclosures: The authors declare no conflict of interest.

Subjects:

Keywords:

  • Immune system
  • Cytokines
  • Inflammation
  • Brain
  • Behavior
  • Neuropsychiatric Disorders

Immune system to brain signaling: Neuropsychopharmacological implications

Tools:

Journal Title:

Pharmacology and Therapeutics

Volume:

Volume 130, Number 2

Publisher:

, Pages 226-238

Type of Work:

Article | Post-print: After Peer Review

Abstract:

There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its down stream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appear to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations.

Copyright information:

© 2011 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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