Neurological Disorders

Possible Contribution of Microglial Glutamate Receptors to Inflammatory Response upon Neurodegenerative Diseases

Abstract

Mami Noda and Kaoru Beppu

Microglial cells actively contribute to tripartite synapses by direct contact or releasing diffusible factors. In neuronmicroglia interaction, there are number of candidates as microglial signalling to neurons, for example neurotrophic factors, pro-inflammatory cytokines and chemokines. However, little is known about neuronal signalling to microglia. Microglial cells express various kinds of neurotransmitter receptors including glutamate receptors; both ionotropic and metabotropic glutamate receptors. Among them, microglial AMPA receptors are impermeable to Ca2+ due to the expression of GluA2. GluA2 is an important subunit in determining the functional properties of AMPA receptors, such as Ca2+ -permeability, conductance, assembly and trafficking. Activation of microglia induces membrane translocation of GluA2, while internalization of other subunits occurs, and nearly homomeric GluA2 subunits are suggested as the main reason for low conductance of AMPA receptors in activated microglia. Since low expression of GluA2 was reported in some neurodegenerative diseases, lack of GluA2 in microglia as well as in neurons contribute to excitotoxicity by excess release of proinflammatory cytokines such as TNF-α. Therefore, involvement of microglia in glutamatergic synaptic transmission may be also important to understand the mechanism of some neurodegeneration in which low GluA2 is suggested.