Ketone Body Mediated Modulation of GABAergic Signa.. (KBMMGABA)
Ketone Body Mediated Modulation of GABAergic Signaling: Mechanisms and Consequences
Start date: Mar 2, 2009,
End date: Mar 1, 2011
"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."
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