Article

Immune system to brain signaling: Neuropsychopharmacological implications

Laboratory of Nutrition and Integrative Neurobiology, NutriNeuro, INRA UMR 1286, University Victor Segalen Bordeaux 2, Bordeaux, France.
Pharmacology [?] Therapeutics (Impact Factor: 7.75). 02/2011; 130(2):226-38. DOI: 10.1016/j.pharmthera.2011.01.014
Source: PubMed

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 downstream 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 appears 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.

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Available from: Andrew H Miller, Dec 22, 2013
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    • "The inflammatory activity has been shown to be associated with cognitive performance in obese women [10]. The role of neuroinflammation and cytokines in mood disorders and cognitive impairment have also been demonstrated by both animal studies [11– 13]) and clinical data [14] [15]. "
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    • "(Neurauteretal.,2008).Cytokine-inducedGTP-CH1activation, classicallyassessedbymeasuringincreasedproduction ofneopterin,isindeedabletoimpairthedopaminergic neurotransmission(FelgerandMiller,2012)whichisknown tobeinvolvedinmooddisordersandcognitivedysfunctions, includinginconditionsofchronicimmunestimulation(Brydon etal.,2008;Capuronetal.,2012).Consistentwiththese findings,reducedBH4levelshavebeenreportedinpatients withpsychiatricdisorders(Hashimotoetal.,1994;Hoekstra etal.,2001).Similarly,increasedbloodneopterinconcentrations correlatewithagreaterincidenceofdepressiveepisodesin patientswithmajordepression(Celiketal.,2010).Interestingly, chroniclow-gradeinflammationthatisclassicallyreportedin elderlypeopleisassociatedwithactivationofbothIDOandGTP- CH1(Oxenkrug,2010;Capuronetal.,2011b).Moreimportantly, theseenzymaticactivationshavebeenshowntoparticipatein thepathophysiologyofneuropsychiatricsymptoms,whose prevalenceisoftenhighinagedpopulation(Oxenkrug, 2010;Capuronetal.,2011b).Ofnote,inadditiontoimpair monoaminergicneurotransmission,bothenzymescontributes toincreaseoxidativestress(FelgerandMiller,2012;Stoneetal., 2012;Campbelletal.,2014).Increasedneopterinlevelshave beenreportedinobeserats(Finkelsteinetal.,1982)andhumans (Ledochowskietal.,1999;Oxenkrugetal.,2011),suggesting thatactivationoftheGTP-CH1enzymebycytokines,andthe consequentalterationsofdopamineneurotransmission,may contributetothedevelopmentofneuropsychiatricsymptoms reportedinobesity.Althoughthisassumptionstillneedstobe confirmed,itisworthmentioningthatalterationsofdopamine function,togetherwithalterationsinbasalganglia/reward circuitryhavebeenreportedinobesepatients(deWeijeretal., 2011;Volkowetal.,2011).Moreover,depressive-likebehavior isassociatedinDIOmicewithalterationsinstriatalcircuitry, supportingarolefordopamine-relateddisruptionsinobesityassociateddepressivesymptoms(SharmaandFulton ,2013). "
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