title: The Modulatory Effect of Metabotropic Glutamate Receptor Type-1α on Spike-Wave Discharges in WAG/Rij Rats.
abstract: Modulatory function of metabotropic glutamate type 1 (mGlu1) receptors plays a crucial role in the pathophysiology of some neurological disorders, including schizophrenia and epilepsy. In this study, the expression of mGlu1α receptors in the thalamic nuclei was assessed during development of absence seizures in the WAG/Rij rats, a valid genetic animal model of absence epilepsy. In addition, the effect of pharmacological modulation of mGlu1α receptors in the laterodorsal (LD) nucleus of the thalamus on the characteristic features of bioelectrical brain activities in the WAG/Rij rats was assessed. The expression of mGlu1α receptors in the LD was assessed in four experimental groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. Agonist and antagonist of mGlu1α receptors were infused in LD in the six months old WAG/Rij (epileptic) rats. The protein level of mGlu1α receptors in the thalamus of the 6-month-old WAG/Rij rats was lower than non-epileptic animals. In addition, the distribution of mGlu1α receptors in different thalamic nuclei was lower in the 6-month-old WAG/Rij compared to age-matched Wistar rats. The gene expression of mGlu1α receptor was also significantly lower in 6-month-old WAG/Rij rats in the LD compared to other animal groups. The microinjection of mGlu1α receptors agonist and antagonist in the LD reduced the duration of spike-wave discharges (SWDs) and increased the amplitude and duration of SWDs, respectively, in 6-month-old WAG/Rij rats. The alterations of mGlu1α receptors expression in the thalamus of epileptic WAG/Rij rats as well as its modulatory effects in the generation of SWDs suggest the potential of mGlu1 receptors as a therapeutic target in absence epilepsy.
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.|Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Karimzadeh
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: Sayed Mostafa
authors.initials: SM
authors.lastname: Modarres Mousavi
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Ghadiri
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Jafarian
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shahin Mohammad
authors.initials: SM
authors.lastname: Sadeghi
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, Westfälische Wilhelms-Universität Münster, Münster, Germany.|Klinik und Poliklinik für Neurologie, Westfälische Wilhelms-Universität Münster, Münster, Germany.|Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mesgari
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran. gorjial@uni-muenster.de.|Klinik und Poliklinik für Neurochirurgie, Westfälische Wilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.|Klinik und Poliklinik für Neurologie, Westfälische Wilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.|Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: Brain; Epilepsy; Genetic models of epilepsy; Seizures; Spike-wave discharges