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Ketone Body Mediated Modulation of GABAergic Signaling: Mechanisms and Consequences

Objective

The brain’s high metabolic requirements mean that the mantra of nutritionists worldwide, “You are what you eat!” could be more accurately phrased, “you are what your brain metabolises!”. While glucose provides the major source of energy for the brain, ketone bodies (KBs) also play a critical role during the neonatal period, during fasting and during periods of metabolic stress (1,2,3). The ability of KBs to powerfully modulate neuronal activity is highlighted by the fact that the ketogenic diet has been used for the management of “difficult -to-control” seizures since the 1920s (4,5), and is currently undergoing trials for the management of a variety of neurodegenerative disorders (6). However, neither the molecular mechanisms by which ketone bodies act, nor the role of KBs during normal development and physiology are known. In vitro studies in a wide variety of animal species and brain structures, indicate that GABAergic signalling is depolarising during the early neonatal period (7). However, preliminary results, in vitro and in vivo, suggest that KBs induce a decrease in [Cl-]i and consequently a hyperpolarising shift in GABAergic signalling in neonates. In this project we will study both the mechanisms of this KB mediated effect and its consequences for neuronal network activity in vivo.

Field of science

  • /medical and health sciences/basic medicine/physiology

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITE DE LA MEDITERRANEE D'AIX-MARSEILLE II
Address
Boulevard Charles Livon, Jardin Du Pharo 58
13284 Marseille
France
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 165 444,54
Administrative Contact
Celine Damon (Ms.)