Published online Jun 28, 2018. doi: 10.5498/wjp.v8.i2.51
Peer-review started: March 19, 2018
First decision: May 8, 2018
Revised: May 15, 2018
Accepted: June 8, 2018
Article in press: June 9, 2018
Published online: June 28, 2018
Glutamate is the predominant excitatory neurotransmitter in the human brain and it has been shown that prolonged activation of the glutamatergic system leads to nerve damage and cell death. Following release from the pre-synaptic neuron and synaptic transmission, glutamate is either taken up into the pre-synaptic neuron or neighbouring glia by transmembrane glutamate transporters. Excitatory amino acid transporter (EAAT) 1 and EAAT2 are Na+-dependant glutamate transporters expressed predominantly in glia cells of the central nervous system. As the most abundant glutamate transporters, their primary role is to modulate levels of glutamatergic excitability and prevent spill over of glutamate beyond the synapse. This role is facilitated through the binding and transportation of glutamate into astrocytes and microglia. The function of EAAT1 and EAAT2 is heavily regulated at the levels of gene expression, post-transcriptional splicing, glycosylation states and cell-surface trafficking of the protein. Both glutamatergic dysfunction and glial dysfunction have been proposed to be involved in psychiatric disorder. This review will present an overview of the roles that EAAT1 and EAAT2 play in modulating glutamatergic activity in the human brain, and mount an argument that these two transporters could be involved in the aetiologies of schizophrenia and affective disorders as well as represent potential drug targets for novel therapies for those disorders.
Core tip: Following release from the presynaptic neuron, the majority of glutamate within the human cortex is taken up into glia cells where it is converted into glutamine for recycling back into glutamate. Glutamate transporters excitatory amino acid transporter (EAAT) 1 and EAAT2 are predominantly localized in the glial plasma membrane, and are responsible for the majority of glutamate uptake within the human brain. Here we provide a comprehensive review of the unique regulation of EAAT1 and EAAT2 mRNA and protein in health and psychiatric disorder, and in response to medication use.