Doxycycline could aggravate the absence-like epileptic seizures of WAG/Rij rats via matrix metalloproteinase inhibition

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Abstract

Matrix metalloproteinases (MMPs) are known to be activated in the brain by epileptic seizures and elevated MMP-9 activity has been found in a genetic model of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In this study we posed the question, whether MMP inhibitory dose of doxycycline (20 mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20 mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4 h. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10 mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl-l- tryptophane methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10 mg/kg doxycycline significantly increased the SWD number for 1 h, GM6001 significantly increased the SWD number during the whole 4-h recording period. Our results could indicate that the induction of MMPs in the epileptic brain, besides contributing to structural remodeling, would also be associated with such functions as homeostatic synaptic plasticity which might counteract epileptic seizures.

Original languageEnglish
Pages (from-to)563-566
Number of pages4
JournalNeurochemistry International
Volume59
Issue number5
DOIs
Publication statusPublished - okt. 2011

Fingerprint

Doxycycline
Matrix Metalloproteinases
Epilepsy
Absence Epilepsy
Generalized Epilepsy
Neuronal Plasticity
Matrix Metalloproteinase Inhibitors
Genetic Models
Matrix Metalloproteinase 9
Brain
Anti-Inflammatory Agents
Incidence
N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

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title = "Doxycycline could aggravate the absence-like epileptic seizures of WAG/Rij rats via matrix metalloproteinase inhibition",
abstract = "Matrix metalloproteinases (MMPs) are known to be activated in the brain by epileptic seizures and elevated MMP-9 activity has been found in a genetic model of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In this study we posed the question, whether MMP inhibitory dose of doxycycline (20 mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20 mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4 h. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10 mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl-l- tryptophane methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10 mg/kg doxycycline significantly increased the SWD number for 1 h, GM6001 significantly increased the SWD number during the whole 4-h recording period. Our results could indicate that the induction of MMPs in the epileptic brain, besides contributing to structural remodeling, would also be associated with such functions as homeostatic synaptic plasticity which might counteract epileptic seizures.",
keywords = "Absence epilepsy, Doxycycline, Matrix metalloproteinases, WAG/Rij rats",
author = "Z. Kov{\'a}cs and K. K{\'e}kesi and P{\'e}ter Baracskay and G. Juh{\'a}sz and A. Czurk{\'o}",
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language = "English",
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T1 - Doxycycline could aggravate the absence-like epileptic seizures of WAG/Rij rats via matrix metalloproteinase inhibition

AU - Kovács, Z.

AU - Kékesi, K.

AU - Baracskay, Péter

AU - Juhász, G.

AU - Czurkó, A.

PY - 2011/10

Y1 - 2011/10

N2 - Matrix metalloproteinases (MMPs) are known to be activated in the brain by epileptic seizures and elevated MMP-9 activity has been found in a genetic model of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In this study we posed the question, whether MMP inhibitory dose of doxycycline (20 mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20 mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4 h. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10 mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl-l- tryptophane methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10 mg/kg doxycycline significantly increased the SWD number for 1 h, GM6001 significantly increased the SWD number during the whole 4-h recording period. Our results could indicate that the induction of MMPs in the epileptic brain, besides contributing to structural remodeling, would also be associated with such functions as homeostatic synaptic plasticity which might counteract epileptic seizures.

AB - Matrix metalloproteinases (MMPs) are known to be activated in the brain by epileptic seizures and elevated MMP-9 activity has been found in a genetic model of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In this study we posed the question, whether MMP inhibitory dose of doxycycline (20 mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20 mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4 h. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10 mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl-l- tryptophane methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10 mg/kg doxycycline significantly increased the SWD number for 1 h, GM6001 significantly increased the SWD number during the whole 4-h recording period. Our results could indicate that the induction of MMPs in the epileptic brain, besides contributing to structural remodeling, would also be associated with such functions as homeostatic synaptic plasticity which might counteract epileptic seizures.

KW - Absence epilepsy

KW - Doxycycline

KW - Matrix metalloproteinases

KW - WAG/Rij rats

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