Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn-1 gene.

Autor: Batten SR; Department of Psychology University of Kentucky College of Arts and Sciences Lexington KY USA., Matveeva EA; Department of Molecular & Cellular Biochemistry University of Kentucky Medical Center Lexington KY USA., Whiteheart SW; Department of Molecular & Cellular Biochemistry University of Kentucky Medical Center Lexington KY USA., Vanaman TC; Department of Molecular & Cellular Biochemistry University of Kentucky Medical Center Lexington KY USA., Gerhardt GA; Department of Neuroscience University of Kentucky Medical Center Lexington KY USA.; Department of Neurology University of Kentucky Medical Center Lexington KY USA., Slevin JT; Neurology Service Veterans Affairs Medical Center Lexington KY USA.; Department of Neurology University of Kentucky Medical Center Lexington KY USA.; Department of Pharmacology and Nutritional Sciences University of Kentucky Medical Center Lexington KY USA.
Jazyk: angličtina
Zdroj: Brain and behavior [Brain Behav] 2017 Aug 13; Vol. 7 (9), pp. e00795. Date of Electronic Publication: 2017 Aug 13 (Print Publication: 2017).
DOI: 10.1002/brb3.795
Abstrakt: Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling.
Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1 -/- (Tom -/- ) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA).
Results: Naïve Tom -/- mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as measured by MEA of presynaptic release in the hippocampal dentate gyrus (DG). Kindling progression was considerably accelerated in Tom -/- mice, requiring fewer stimuli to reach a fully kindled state. Following full kindling, MEA measurements of both kindled Tom +/+ and Tom -/- mice showed significant increases in KCl-evoked and spontaneous glutamate release in the DG, indicating a correlation with the fully kindled state independent of genotype. Resting glutamate levels in all hippocampal subregions were significantly lower in the kindled Tom -/- mice, suggesting possible changes in basal control of glutamate circuitry in the kindled Tom -/- mice.
Conclusions: Our studies demonstrate that increased glutamate release in the hippocampal DG correlates with acceleration of the kindling process. Although STXBP5/tomosyn-1 loss increased evoked glutamate release in naïve animals contributing to their prokindling phenotype, the kindling process can override any attenuating effect of STXBP5/tomosyn-1. Loss of this "braking" effect of STXBP5/tomosyn-1 on kindling progression may set in motion an alternative but ultimately equally ineffective compensatory response, detected here as reduced basal glutamate release.
Databáze: MEDLINE
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