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 (20mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4h. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10mg/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 10mg/kg doxycycline significantly increased the SWD number for 1h, 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.
authors: Department of Zoology, University of West Hungary, Savaria Campus, Szombathely, Hungary. zskovacs@ttk.nyme.hu
authors: Zsolt
authors: Z
authors: Kovács
authors: Katalin A
authors: KA
authors: Kékesi
authors: Péter
authors: P
authors: Baracskay
authors: Gábor
authors: G
authors: Juhász
authors: András
authors: A
authors: Czurkó
mesh_terms: D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000139:chemically induced* / Q000201:enzymology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D009473:Neuronal Plasticity / Q000187:drug effects; D011480:Protease Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004151:Dipeptides; D018690:Excitatory Amino Acid Agonists; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D004318:Doxycycline; D007608:Kainic Acid