PET imaging of glutamate metabolism

glutamic acid

L-Glutamate is an abundant amino acid, and a major constituent of proteins.

L-Glutamate is also the predominant excitatory neurotransmitter in the glutamatergic system in central nervous system. Glutamate is concentrated in presynaptic vesicles by active transporters (VGluTs). Glutamate that is released into the synapse is sequestered into neurons and glia by high-affinity glutamate transporters, and metabolized by astrocytes to glutamine. In the presence of decreased extracellular Na+ these transporters can function in reverse, releasing glutamate to the extracellular space.

Cystine/glutamate antiporter (system xC-) is vital to antioxidant defence in the brain, and its expression and activity is rapidly upregulated under oxidative stress. Glutamate released by system xC- activates extrasynaptic, but not synaptic, NMDA iGluRs. During brain ischaemia, an excessive release of glutamate triggers neuronal death through the over-activation of NMDA iGluRs. EPO can block glutamate release and prevent cell death. PET imaging with [18F]FSPG has shown increased xC- function in ischaemic rats (Soria et al., 2014; Domercq et al., 2016) and in rat model of MS (Martín et al., 2016).

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Updated at: 2023-01-28
Created at: 2015-08-26
Written by: Vesa Oikonen