Modulation of Glutamate Receptor Expression in Health and Disease

Glutamate is a neuronal excitatory transmitter found abundantly within the hippocampus that has vital functions rooted in learning, memory, and cognition. Overabundance or improper regulation of glutamate can have detrimental effects on neuronal function, with previous research indicating its implications in the progression of Alzheimer’s disease. Specifically, a portion of Alzheimer’s disease pathology is connected directly to increased levels of the amyloid plaque buildup in the postsynaptic space, leading to impairment in glutamate clearance by astrocytic glutamate transporters GLT-1 and GLAST. Amyloid plaques are just one of many contributors to the progression of Alzheimer’s disease, with circadian rhythm disruption being another. Circadian rhythm refers to the body’s internal “biological clock” and regulates environmental, hormonal, and behavioral changes within a 24-h period. These circadian rhythms are controlled by clock genes located in the suprachiasmatic nucleus as well as in other portions of the brain, such as the hippocampus. The activation of NMDA glutamate receptors found in CA1 pyramidal cells in the hippocampus may have circadian oscillations, with subunits GluN1, GluN2A, and GluN2B contributing to the regulation of synaptic transmissions and events. The expression of these subunits at differing light cycles: light/dark vs. dark/dark may provide insight into the circadian modulation of these glutamate receptors. The modulation of glutamate by differing mechanisms, such as increased amyloid plaques and disrupted circadian cycles, can provide insight into the onset of AD and the implication of glutamate-related neurotoxicity in its pathology.