The contribution of astrocytes to the ¹⁸F-2-deoxyglucose signal in PET activation studies

With the development of functional brain imaging techniques such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) it has become possible to visualize brain areas that are activated by a variety of sensory, motor or cognitive tasks. This technological progress has permitted a kind of in vivo functional neuroanatomy which has led to the identification of neural circuits subserving specific brain functions. Metabolic processes linked to neuronal activity - such as blood flow, glucose utilization and oxygen consumption - provide the signals detected with most functional brain-imaging techniques. These metabolic indices have been examined in a variety of psychiatric and neurological disorders. This article focuses on the use of (¹⁸F)fluoro-2-deoxyglucose (FDG)-PET in the study of psychiatric disorders; it is mainly intended to bring a novel perspective, based on recent experimental data, on the cellular and molecular mechanisms that underlie the FDG-based PET imaging. These new observations point to a critical role of a particular glial cell type, the astrocyte, in coupling neuronal activity to glucose utilization. Indeed it appears that in response to glutamate released by active neurons, glucose is predominantly taken up by specialized astrocytic processes, the end-feet, which surround brain capillaries; 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. This perspective may also provide renewed insights for the interpretation of FDG-PET studies in psychiatric disorders.