Mécanismes cellulaires du métabolisme énergétique cérébral : implications pour l'imagerie fonctionnelle.

Abstract

Les signaux detectes par les differentes techniques d' imagerie fonctionnelle cerebrale sont fondes sur le couplage activite cerebrale-metabolisme energetique. La tomographie par emission de positons (TEP) et l' imagerie par resonance magnetique permettent de visualiser les aires cerebrales activees. Malgre le degre de sophistication des methodes d' imagerie, la nature precise des mecanismes moleculaires et des types cellulaires impliques dans le couplage entre activite neuronale et consommation d' energie est encore mal connue. La disposition et les relations cytologiques des astrocytes soulignent l' importance de ces cellules dans le metabolisme energetique cerebral. Les astrocytes peuvent detecter l' activite synaptique par le biais de recepteurs et de sites de recaptage pour les neurotransmetteurs (notamment le glutamate, neurotransmetteur excitateur predominant dans le cerveau) et la coupler a une augmentation du metabolisme energetique. Chez l' homme, l' hypothese selon laquelle les signaux detectes pendant l' activation physiologique par la technique de TEP-fluorodesoxyglucose refleterait un captage du traceur par les astrocytes apporte une base cellulaire et moleculaire a certaines des techniques d' imagerie fonctionnelle cerebrale.

Signals detected with functional brain imaging techniques are based on the coupling of neuronal activity with energy metabolism. Techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) allow the visualization of brain areas that are activated by a variety of sensory, motor or cognitive tasks. Despite the technological sophistication of these brain imaging techniques, the precise mechanisms and cell types involved in coupling and in generating metabolic signals are still debated. Recent experimental data on the cellular and molecular mechanisms that underlie the fluorodeoxyglucose (FDG) - based PET imaging point to a critical role of a particular brain cell type, the astrocytes, in coupling neuronal activity to glucose utilization. Indeed, astrocytes possess receptors and re-uptake sites for a variety of neurotransmitters, including glutamate, the predominant excitatory neurotransmitter in the brain. In addition, astrocytic end-feet, whichsurround capillaries, are enriched in the specific glucose transporter GLUT-1. These features allow astrocytes to "sense" synaptic activity and to couple it with energy metabolism. In vivo and in vitro data support the following functional model: in response to glutamate released by active neurons, glucose is predominantly taken up by astrocytic end-feet; glucose is then metabolized to lactate which provides a preferred energy substrate for neurons. These data support the notion that astrocytes markedly contribute to the FDG-PET signal.