Tiagabine suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers.

Autor: Javaid S; Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan; Department of Pharmacy, The Women University, Multan 60000, Pakistan., Alqahtani F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: afaleh@ksu.edu.sa., Ashraf W; Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan., Anjum SMM; The Institute of Pharmaceutical Sciences, University of Veterinary & Animal Sciences, Lahore 75270, Pakistan., Rasool MF; Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan., Ahmad T; Institut pour l'Avancée des Biosciences, Centre de Recherche UGA / INSERM U1209 / CNRS 5309, Université Grenoble Alpes, France., Alasmari F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alasmari AF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alqarni SA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Imran I; Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan. Electronic address: imran.ch@bzu.edu.pk.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Apr; Vol. 160, pp. 114406. Date of Electronic Publication: 2023 Feb 13.
DOI: 10.1016/j.biopha.2023.114406
Abstrakt: Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.5, 1 and 2 mg/kg) for 21 days with simultaneous PTZ (40 mg/kg) injection every other day for a total of 11 injections and monitored for seizure progression with synchronized validation through EEG recordings from cortical electrodes. The post-kindling protection from anxiety and memory deficit was verified by a battery of behavioral experiments. Isolated brains were evaluated for oxidative alterations and real-time changes in mRNA expression for BDNF/TrkB, GAT-1 and GAT-3 as well as neuroinflammatory markers. Experimental results revealed that Tia at the dose of 2 mg/kg maximally inhibited the development of full bloom seizure and reduced epileptic spike discharges from the cortex. Furthermore, Tia dose-dependently exerted the anxiolytic effects and protected from PTZ-evoked cognitive impairment. Tia reduced lipid peroxidation and increased superoxide dismutase and glutathione levels in the brain via augmentation of GABAergic modulation. PTZ-induced upregulated BDNF/TrkB signaling and pro-inflammatory cytokines were mitigated by Tia with upregulation of GAT-1 and GAT-3 transporters in whole brains. In conclusion, the observed effects of Tia might have resulted from reduced oxidative stress, BDNF/TrkB modulation and mitigated neuroinflammatory markers expression leading to reduced epileptogenesis and improved epilepsy-related neuropsychiatric effects.
Competing Interests: Conflict of interest statement The authors declare no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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