Abstract :
Astrocytes represent a quantitatively important cell type of the brain, (at least 50% of the brain volume). Astrocytic profiles, the end-feet, surround intraparenchymal capillaries, implying that they form the first cellular barrier for glucose entering the brain parenchyma. Other astrocyte processes ensheat synapses and possess receptors and reuptake sites for neurotransmitters. These features imply that astrocytes are positioned to sense synaptic activity and to couple it with energy metabolism. Astrocytes may also sense glucose blood levels and modulate neuronal activity accordingly. Evidence for both roles of astrocytes is emerging (Magistretti et al 1995, in Psychopharmacology: The Fourth Generation of Progress, 657-670). Thus, we have shown that in primary astrocyte cultures, noradrenaline (NA) and the peptide VIP promote glycogenolysis (within 0.5 - 3 min), followed by a massive glycogen resynthesis and induction of gene expression (4 to 8 hours). The induced genes are: (i) glycogen synthase and (ii) C/EBP δ, an immediate-early gene involved in energy metabolism regulation. We have also shown that glutamate, in addition to its effects on neuronal excitability, stimulates glucose uptake into astrocytes. Since glutamate is the principal excitatory neurotransmitter of the brain, released from activated afferents to a given cortical area, glutamate-evoked glucose uptake provides a direct link to couple neuronal activity to energy metabolism. It also supports the notion that the 18f-deoxyglucose signal detected in activation PET studies is predominantly localized in astrocytes. Astrocytes may also be involved in glucose sensing in the brain. Thus, the glucose transporter type 2 which has the kinetic properties for glucose sensing, has been identified in astrocytes, particularly in regions involved in energy balance and feeding behavior.
