Figure 3.

Glu is released by vesicles within presynaptic neurons upon excitation, and activates various ionotropic and metabotropic receptors on presynaptic and postsynaptic neurons and glial cells upon release. Astrocytes transport and clear glutamate through highly efficient EAAT. In the cytoplasm, glutamate is converted to Gln, which is exported and taken up by neurons and hydrolyzed to glutamate by glutaminase. (1) Inflammation in the brain limits the ability of the astrocytes to clear spilled glutamate. (2) Excessive glutamate release reduces the amount and function of EAAT. (3) In cells undergoing inflammation, glutamate release from the extracellular space is increased, inducing intercellular Ca²⁺ signaling and the down-regulation of Cx43 gap junctions. (4) The glutamate transporter is altered and the normal production of BDNF is affected. Glu, Glutamate; Gln, glutamine; HC, hemichannel; GJC, gap junction channels; EAAT, excitatory amino acid transporter; AMPAR, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; NMDAR, N-methyl-D-aspartate-receptor; mGluR₅, metabotropic glutamate receptor 5; BDNF, brain-derived neurotrophic factor.