The Role of Glutamate Receptors in Epilepsy

Abstract

Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing.

Targeting glutamate metabolism in chronic lung diseases

“…Group III mGluRs (mGluR4, mGluR6, mGluR7 and mGluR8) participate in the regulation of neurotransmitter release, modulation of synaptic transmission and have effects on pain perception, addiction and motor coordination. 34,35 Glutamate metabolism is associated with the process of protein folding, de novo synthesis of nucleic acid and lipid synthesis (Figure 3). As a common neurotransmitter, glutamate is intricately involved in the pathogenesis of numerous neurological disorders, spanning from epileptic seizures and traumatic brain injuries to neurodegenerative diseases and psychiatric disorders.…”

“…Abnormal glutamate release and excitotoxicity can contribute to epileptic seizures. 34 Glutamate-induced excitotoxicity plays a significant role in promoting damage following an ischemic stroke. Ischaemia leads to abnor-mal glutamate release and impaired reuptake, promoting neuronal death.…”

“…Group II mGluRs (mGluR2 and mGluR3) are involved in the regulation of neurotransmitter release, modulation of synaptic transmission and influence processes such as anxiety and cognition. Group III mGluRs (mGluR4, mGluR6, mGluR7 and mGluR8) participate in the regulation of neurotransmitter release, modulation of synaptic transmission and have effects on pain perception, addiction and motor coordination 34,35 …”

Mechanisms of glutamate metabolic function and dysfunction in vascular dementia

“…Both presynaptic and postsynaptic Group II (mGluR 2 and 3) and presynaptic Group III (mGluR 4, 6, 7, and 8) act as autoreceptors by regulating the release characteristics of glutamate in an activity‐dependent manner 80,81 . Activation of mGluRs in the central nervous system facilitates or inhibits AMPA and NMDA receptor responses to glutamate by regulating K + and Ca 2+ ion channels 64,78 . mGluRs play a crucial role in mediating synaptic plasticity and neurotransmitter transmission.…”

Nano‐delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives

“… Altered expression of transporters: The BBB in epilepsy also has altered expression of transporters, which are proteins that help regulate molecules' movement across the BBB. This altered expression can lead to imbalances in the levels of certain nutrients and chemicals in the brain, which can contribute to seizures 12 Neuroinflammation: Neuroinflammation is a common feature of epilepsy and can also contribute to BBB dysfunction.…”