Notes

Energy Metabolism Astrocytes are very nicely located to take up blood vessels energy substrates. They do so through GLUT1, which brings glucose into the astrocytes. Then, a cascade of metabolic processes takes place which brings to the formation of Lactate. The Lactate is then shuttled to neurons. We have to realize that glucose can also directly be delivered to neurons without the need of astrocytes to process it. Oxygen is passively diffused (it is not an active transport) through the entire tissue, with a high oxygen pressure in the vessel. All of the Lactate transport follows the chemical gradient, which implies that the astrocytes have an higher concentration of Lactate than neurons, which allows the flow.

Neurotransmission Glutamate released from the neuron is taken up by astrocytes. If this process fails, a lack of astrocytic uptake of Glutamate leads to hyperexcitability. Also, GABA is mostly taken up by astrocytes.

• Glutamate-Glutamine Shuttle
  • Synaptic glutamate is taken up through excitatory amino acid transporters (EAATs).
  • Astrocytes either convert it to glutamine (via glutamine synthase, only present in the astrocytes) or intermediates of the TCA cycle.
  • Glutamine is transported back to neurons.
• GABA
  • GABA is taken up through GABA transporters (GATs).
  • It enters the TCA cycle.

Biosynthesis The nervous system always needs to form a lot of new stuff, which are provided in a large extent from astrocytic metabolism. In neurons, this is mainly done through Glutamate uptake.

• Glucose: diverted through the astrocytic PPP generates NADPH and precursors for the synthesis of nucleotides and amino acids.
• Pyruvate: carboxylated into the Krebs cycle intermediate oxalo-acetate (OAA), which is a precursor of multiple biosynthetic pathways in astrocytes and, through shuttling of glutamine, is also the main precursor for neuronal biosynthesis.

Waste Recycling Astrocytic waste recycling is extremely important, tons of stuff happening to make sure that the neuron well-being is maintained. Astrocytes buffer potassium (very important), to avoid that there are excessive potassium ions which need to be cleared. K+ ATPase pumps potassium ions into astrocytes. Another major thing is the scavenge reactive oxygen species produced in many processes in the neuron happens through astrocytes.

• Reactive Oxygen Species (ROS) in neurons are scavenged by ascorbate (AA) with the production of dehydroascorbic acid (DHA), which diffuses through the glucose transporters toward astrocytes to be recycled into AA, and is returned to neurons via anion channels and the SVCT2. Glutathione (GSH) reacts with ROS to generate glutathione disulfide (GSSG), or with xenobiotics to generate conjugated glutathione (GS-X), both of which are discarded via multidrug resistance proteins (MDR). GSH synthesized and released by astrocytes is cleaved in the interstice to cysteine, which controls the neuronal synthesis of GSH. Ammonia (NH3) released by the deamidation of glutamine into glutamate leaves neurons by an unknown pathway and is captured as ammonium (NH4), where it is recycled by glutamine synthase. K+ released by neurons during synaptic activity enters astrocytes via K+ channels and the Na+/K+ ATPase. Methylglyoxal is a side product of glycolysis, which is detoxified mostly in astrocytes by the glyoxalase system.