Astroglial Glutamine Synthetase and the Pathogenesis of Mesial Temporal Lobe Epilepsy.

Mani Ratnesh S Sandhu,Tore Eid,Ketaki Deshpande,Tih-Shih W Lee,Roni Dhaher,Hitten P Zaveri,Benjamin F Gruenbaum,Shaun E Gruenbaum,Melissa C Funaro

doi:10.3389/fneur.2021.665334

Abstract

The enzyme glutamine synthetase (GS), also referred to as glutamate ammonia ligase, is abundant in astrocytes and catalyzes the conversion of ammonia and glutamate to glutamine. Deficiency or dysfunction of astrocytic GS in discrete brain regions have been associated with several types of epilepsy, including medically-intractable mesial temporal lobe epilepsy (MTLE), neocortical epilepsies, and glioblastoma-associated epilepsy. Moreover, experimental inhibition or deletion of GS in the entorhinal-hippocampal territory of laboratory animals causes an MTLE-like syndrome characterized by spontaneous, recurrent hippocampal-onset seizures, loss of hippocampal neurons, and in some cases comorbid depressive-like features. The goal of this review is to summarize and discuss the possible roles of astroglial GS in the pathogenesis of epilepsy.

Highlights

Astrocytes have historically been thought to serve a primarily structural role by supporting surrounding neurons [1]
Following an acute central nervous system (CNS) injury, astrocytes undergo several morphological and functional changes. These “reactive astrocytes” are present in several pathological conditions While reactive astrocytes were originally thought to reflect scar tissue in response to neuronal injury and loss, recent studies have suggested that reactive astrocytes may play important roles in the causation of many disorders, including epilepsy [18,19,20]
Glutamine synthetase (GS, known as glutamate-ammonia-ligase, EC 6.3.1.2), an enzyme that is highly abundant in astrocytes, is of particular interest due to its roles in health and disease [21]

Summary

Introduction

Astrocytes have historically been thought to serve a primarily structural role by supporting surrounding neurons [1]. Following an acute central nervous system (CNS) injury, astrocytes undergo several morphological and functional changes These “reactive astrocytes” are present in several pathological conditions While reactive astrocytes were originally thought to reflect scar tissue in response to neuronal injury and loss, recent studies have suggested that reactive astrocytes may play important roles in the causation of many disorders, including epilepsy [18,19,20]. Studies have further suggested that acquired GS deficiencies in discrete areas of the brain might play a causative role in various neurological disorders and psychiatric conditions including Alzheimer’s disease, hepatic encephalopathy, Glutamine Synthetase in Epilepsy suicide/depression schizophrenia, and epilepsy [24,25,26,27,28,29,30,31,32]. The goal of this review is to discuss the significance of GS in the pathogenesis of focal epilepsies, mesial temporal lobe epilepsy (MTLE), which is one of the most common types of medication-refractory epilepsies in humans [26, 32,33,34,35]

Objectives

Conclusion