Neuroprotective effects of energy substratesAdmin

Not only ketone bodies

A shortage of ketones caused pathological changes in brain cells in brain slices (in vitro, 1) and in whole animals (in vivo, 2) resulting in abnormal (excitatory) behavior of GABA, the principal brain chemical helping to resist hyperactivity. In the article (1), the authors showed that not only ketone bodies, but also other energy carriers such as lactate and pyruvate (or their shortages) can make all the difference between smoothly functioning brain networks and pathologically overly excited ones.

In the doctoral thesis (2), GABA action in the brain of immature rats was always inhibitory, however, blockade of ketogenesis made it less inhibitory.

We suggest that metabolic deficits induce changes in intrinsic neuronal properties resulting in hyperactivity in single neurons and aberrant neuronal network behavior. This hyperactivity in turn increases neuronal energy demands, which cannot be met due to metabolic pathologies and a vicious cycle occurs. Our hypothesis predicts that the adequate delivery of energy substrates may interrupt this pathological spiral of events and provide therapeutic options targeting the cause of pathologies rather than their symptoms” concluded the authors.

Sources:

1. Holmgren CD, Mukhtarov M, Malkov AE, Popova IY, Bregestovski P, Zilberter Y.. Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. J Neurochem. 2010 Feb;112(4):900-12. Epub 2009 Nov 24.

2. Sylvain Rheims. Initiation et modulation des oscillations physiologiques et pathologiques dans le neocortex immature : role de la transmission GABAergique. Faculté des sciences de luminy ecole doctorale de la vie et de la santé. These de doctorat. Pour obtenir le grade de docteur de l’universite aix marseille ii. Spécialité : neurosciences. Le 31 octobre 2008