Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.

Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.
Exp Neurol. 2016 Oct 18;:
Authors: Albright B, Dhaher R, Wang H, Harb R, Lee TW, Zaveri H, Eid T
Abstract
Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE).However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats. We then used continuous video-intracranial electroencephalogram (EEG) monitoring and c-Fos immunohistochemistry to determine the type of seizures and spatial distribution of neuronal activation early (1-5days postinfusion) and late (16-43days postinfusion) in epileptogenesis.Early in epileptogenesis, seizures were preferentially mild (stage 1-2), activating neurons in the entorhinal-hippocampal area, the basolateral amygdala, the piriform cortex, the midline thalamus, and the anterior olfactory area.Late in epileptogenesis, the seizures were generally more severe (stages 4-5) with neuronal activation extending to the neocortex, the bed nucleus of the stria terminalis, the mediodorsal thalamus, an...

Source: Experimental Neurology - October 17, 2016 Category: Neurology Authors: Albright B, Dhaher R, Wang H, Harb R, Lee TW, Zaveri H, Eid T Tags: Exp Neurol Source Type: research