Homeostatic control of brain function – new approaches to understand epileptogenesis
- 1Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR, USA
- 2Department of Psychology and Neuroscience Program, Trinity College, Hartford, CT, USA
- 3Department of Pharmacology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
Neuronal excitability of the brain and ongoing homeostasis depend not only on intrinsic neuronal properties, but also on external environmental factors; together these determine the functionality of neuronal networks. Homeostatic factors become critically important during epileptogenesis, a process that involves complex disruption of self-regulatory mechanisms. Here we focus on the bioenergetic homeostatic network regulator adenosine, a purine nucleoside whose availability is largely regulated by astrocytes. Endogenous adenosine modulates complex network function through multiple mechanisms including adenosine receptor-mediated pathways, mitochondrial bioenergetics, and adenosine receptor-independent changes to the epigenome. Accumulating evidence from our laboratories shows that disruption of adenosine homeostasis plays a major role in epileptogenesis. Conversely, we have found that reconstruction of adenosine’s homeostatic functions provides new hope for the prevention of epileptogenesis. We will discuss how adenosine-based therapeutic approaches may interfere with epileptogenesis on an epigenetic level, and how dietary interventions can be used to restore network homeostasis in the brain. We conclude that reconstruction of homeostatic functions in the brain offers a new conceptual advance for the treatment of neurological conditions which goes far beyond current target-centric treatment approaches.
Keywords: adenosine, glial cells, ketogenic diet, mitochondrial bioenergetics and physiology, DNA methylation, transmethylation pathway, epileptogenesis, homeostasis
Citation: Boison D, Sandau US, Ruskin DN, Kawamura M Jr and Masino SA (2013) Homeostatic control of brain function – new approaches to understand epileptogenesis. Front. Cell. Neurosci. 7:109. doi: 10.3389/fncel.2013.00109
Received: 30 April 2013; Accepted: 22 June 2013;
Published online: 16 July 2013.
, The Hebrew University of Jerusalem, Israel
, Oregon Health and Science University, USA
Copyright: © 2013 Boison, Sandau, Ruskin, Kawamura and Masino. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Detlev Boison, Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, 1225 Northeast 2nd Avenue, Portland, OR 97232, USA e-mail: email@example.com; Susan A. Masino, Department of Psychology and Neuroscience Program, Trinity College, 300 Summit Street, Hartford, CT 06106, USA e-mail: firstname.lastname@example.org