Abstract
The normal physiology of neurons is achieved through a delicate balance between excitatory and inhibitory synapses. Any disruption of such intricate balance can induce neuronal hyper-excitability in a susceptible neuronal network leading to seizures. Glutamate is the main excitatory neurotransmitter in the nervous system but when it is accumulated in excess induces neurotoxicity, mediates neuronal hyper-excitability and seizures. In epilepsy, glutamate is abnormally concentrated in the brain. Such abnormality is related with an altered synthesis, metabolism, storage, exocytosis, and clearance of glutamate. Accumulation of glutamate triggers over-activation of ionotropic N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and 2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine (Kainate) receptors (KAr) as well as metabotropic glutamate receptors (mGLURs) in neurons. In addition, the abnormal molecular signaling from those receptors promotes cell damage and aberrant neuronal plasticity that could participate in the biology mechanism of epilepsy. In addition, glutamate is accumulated in other neurological with high incidence of recurrent epilepsy, such as glioblastoma multiforme and Sturge-Weber syndrome. Dissecting the cellular and molecular biology of glutamatergic system in inducing, propagating, and sustaining seizures will provide a new avenue for an innovative anti-seizure and/or anti-epileptogenenic drugs.
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Musto, A.E. (2022). Glutamate and Epilepsy: An Insight from Temporal Lobe Epilepsy. In: Pavlovic, Z.M. (eds) Glutamate and Neuropsychiatric Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-87480-3_18
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