Pretreatment with a glutamine synthetase inhibitor MSO delays the onset of initial seizures induced by pilocarpine in juvenile rats.

Autor: Pawlik MJ; Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: mpawlik@imdik.pan.pl., Obara-Michlewska M; Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: mobara@imdik.pan.pl., Popek MP; Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: mpopek@imdik.pan.pl., Czarnecka AM; Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: aczarnecka@imdik.pan.pl., Czuczwar SJ; Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: czuczwarsj@yahoo.com., Łuszczki J; Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: jarogniewluszczki@umlub.pl., Kołodziej M; Institute of Theory of Electrical Engineering, Measurement and Information Systems, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland. Electronic address: marcin.kolodziej@ee.pw.edu.pl., Acewicz A; Department of Neuropathology, Institute of Psychiatry and Neurology, Jana III Sobieskiego 9, 02-957 Warsaw, Poland. Electronic address: aacewicz@ipin.edu.pl., Wierzba-Bobrowicz T; Department of Neuropathology, Institute of Psychiatry and Neurology, Jana III Sobieskiego 9, 02-957 Warsaw, Poland. Electronic address: bobrow@ipin.edu.pl., Albrecht J; Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: jalbrecht@imdik.pan.pl.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2021 Feb 15; Vol. 1753, pp. 147253. Date of Electronic Publication: 2021 Jan 07.
DOI: 10.1016/j.brainres.2020.147253
Abstrakt: The contribution of glutamatergic transmission to generation of initial convulsive seizures (CS) is debated. We tested whether pretreatment with a glutamine synthetase (GS) inhibitor, methionine sulfoximine (MSO), affects the onset and progression of initial CS by cholinergic stimulus in juvenile rats. Male rats (24 days old, Sprague Dawley) sequentially received i.p. injections of lithium-carbonate, MSO, methyl-scopolamine, and pilocarpine (Pilo). Pilo was given 150 min after MSO. Animals were continuously monitored using the Racine scale, EEG/EMG and intrahippocampal glutamate (Glu) biosensors. GS activity as measured in hippocampal homogenates, was not altered by MSO at 150 min, showed initial, varied inhibition at 165 (15 min post-Pilo), and dropped down to 11% of control at 60 min post-Pilo, whereas GS protein expression remained unaltered throughout. Pilo did neither modulate the effect of MSO on GS activity nor affect GS activity itself, at any time point. MSO reduced from 32% to 4% the number of animals showing CS during the first 12 min post-Pilo, delayed by ~6 min the appearance of electrographic seizures, and tended to decrease EMG power during ~15 min post-Pilo. The results indicate that MSO impairs an aspect of glutamatergic transmission involved in the transition from the first cholinergic stimulus to the onset of seizures. A continuous rise of extracellular Glu lasting 60 min was insignificantly affected by MSO, leaving the nature of the Glu pool(s) involved in altered glutamatergic transmission undefined.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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