title: Noradrenergic regulation of inflammatory gene expression in brain.
abstract: It is now well accepted that inflammatory events contribute to the pathogenesis of numerous neurological disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, and AID's dementia. Whereas inflammation in the periphery is subject to rapid down regulation by increases in anti-inflammatory molecules and the presence of scavenging soluble cytokine receptors, the presence of an intact blood-brain barrier may limit a similar autoregulation from occurring in brain. Mechanisms intrinsic to the brain may provide additional immunomodulatory functions, and whose dysregulation could contribute to increased inflammation in disease. The findings that noradrenaline (NA) reduces cytokine expression in microglial, astroglial, and brain endothelial cells in vitro, and that modification of the noradrenergic signaling system occurs in some brain diseases having an inflammatory component, suggests that NA could act as an endogenous immunomodulator in brain. Furthermore, accumulating studies indicate that modification of the noradrenergic signaling system occurs in some neurodiseases. In this article, we will briefly review the evidence that NA can modulate inflammatory gene expression in vitro, summarize data supporting a similar immunomodulatory role in brain, and present recent data implicating a role for NA in attenuating the cortical inflammatory response to beta amyloid protein.
authors.affiliation: Department of Anesthesiology, University of Illinois, Chicago, IL, USA. dlfeins@uic.edu
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Feinstein
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Gavrilyuk
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dello Russo
authors.forename: Guy
authors.initials: G
authors.lastname: Weinberg
authors.forename: Elena
authors.initials: E
authors.lastname: Galea
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics* / Q000502:physiology*; D003714:Denervation; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D009638:Norepinephrine / Q000502:physiology*; D058225:Plaque, Amyloid / Q000473:pathology
chemical_list: D009638:Norepinephrine