Noradrenergic Regulation of Glial Activation: Molecular Mechanisms and Therapeutic Implications

• Published in: Current neuropharmacology Vol. 12; no. 4; pp. 342 - 352
• Main Authors: Braun, David, Madrigal, Jose L M, Feinstein, Douglas L
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.07.2014; Bentham Science Publishers
• Subjects: amyloid; Alzheimer’s disease; transgenic mice; multiple sclerosis; review; EAE; noradrenaline; locus coeruleus; GFAP; tyrosine hydroxylase
• ISSN: 1570-159X; 1875-6190
• DOI: 10.2174/1570159x12666140828220938

It has been known for many years that the endogenous neurotransmitter noradrenaline (NA) exerts antiinflammatory and neuroprotective effects both in vitro and in vivo. In many cases the site of action of NA are betaadrenergic receptors (βARs), causing an increase in intracellular levels of cAMP which initiates a broad cascade of events including suppression of inflammatory transcription factor activities, alterations in nuclear localization of proteins, and induction of patterns of gene expression mediated through activity of the CREB transcription factor. These changes lead not only to reduced inflammatory events, but also contribute to neuroprotective actions of NA by increasing expression of neurotrophic substances including BDNF, GDNF, and NGF. These properties have prompted studies to determine if treatments with drugs to raise CNS NA levels could provide benefit in various neurological conditions and diseases having an inflammatory component. Moreover, increasing evidence shows that disruptions in endogenous NA levels occurs in several diseases and conditions including Alzheimer's disease (AD), Parkinson's disease (PD), Down's syndrome, posttraumatic stress disorder (PTSD), and multiple sclerosis (MS), suggesting that damage to NA producing neurons is a common factor that contributes to the initiation or progression of neuropathology. Methods to increase NA levels, or to reduce damage to noradrenergic neurons, therefore represent potential preventative as well as therapeutic approaches to disease.