Affiliations: Department of Pharmacology, Physiology and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND, USA
Note: [] Correspondence to: Thad A. Rosenberger, Ph.D., University of North Dakota, School of Medicine and Health Sciences, 501 North Columbia Road, Room 3742, Grand Forks, ND 58203, USA. Tel.: +1 701 777 0591; Fax: +1 701 777 4490; E-mail: thad.rosenberger@med.und.edu
Abstract: The innate immune response maintains a vital role in the health of the central nervous system. Within the central nervous system the innate immune response is initiated following the binding of antigen to microglia that activates inflammatory cascades within the cell, recruits other microglial cells to the sight of action, and induces reactive astrogliosis of neighboring astrocytes. Under normal circumstance, once the antigen is cleared both the activated microglia and reactive astrocytes return to their quiescent or ramified states. With many neurological diseases and injury, neuroinflammatory cascades become tonically activated resulting in sustained neuroglia activation that can result in the induction, and/or progression of neurological injury. Because neuroinflammation is a key pathological element found in many neurological disorders it is believed that reducing inflammatory events in the brain can reduce injury and slow disease progression. In this regard, acetate supplementation by increasing the intracellular concentration of the metabolically active intermediate acetyl-CoA imparts both anti-inflammatory and neuroprotective properties. In this review, we summarize the current state of knowledge concerning the metabolism of acetate within the central nervous system and explore potential mechanisms of action by which acetate reduces neuroglial activation and neuroinflammatory signaling.
