title: Metabotropic glutamate receptor 2/3 density and its relation to the hippocampal neuropathology in a model of temporal lobe epilepsy in rats.
abstract: Dysregulation in the glutamatergic function is considered a major contributor to hyperexcitatory neuronal networks in mesial temporal lobe epilepsy (MTLE). Studies in animal models of MTLE have shown positive outcomes of augmenting group 2-metabotropic receptor functions that can regulate neuronal excitability from extrasynaptic locations. To assist in efficient translation of these findings to the clinical settings, we aimed to characterise the expression of mGluR2/3 receptors in the brain areas relevant to MTLE. mGluR2/3 density was determined by autoradiographic techniques using [3H]-LY341495 at various cross-sectional timepoints following kainic acid-induced status epilepticus (KASE) covering the acute, latent and chronic phases of epilepsy pathogenesis. We found a significant reduction in the mGluR density in the CA1 and temporal cortex during the acute (2day) timepoint after SE in KASE rats whereas a reduced receptor density was only found in temporal cortex during the latent period (7day). During the late latent phase (14day), a generalised increase in the receptor density was found in widely distributed brain areas of KASE rats. Finally, in the chronic periods (day 42 and 84) a significant decrease was seen in the stratum lacunosum moleculare in the KASE rats. Moreover, mGluR2/3 density in the CA1 regions strongly correlated with the neuronal cell scores in the hippocampal regions. Our findings suggest a time dependent evolving pattern of mGluR2/3 density during the pathogenesis of MTLE and provide insights for utilising this data for in vivo imaging to predict the specific timepoints and responsiveness to the therapy targeting mGluR2/3.
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium. Electronic address: idrish.ali@uantwerpen.be.
authors: Idrish
authors: I
authors: Ali
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium.
authors: Stephanie
authors: S
authors: Boets
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium.
authors: Pieter
authors: P
authors: Janssens
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium.
authors: Annemie
authors: A
authors: Van Eetveldt
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium.
authors: Halima
authors: H
authors: Amhaoul
authors: Janssen Research and Development, Beerse, Belgium.
authors: Xavier
authors: X
authors: Langlois
authors: Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium. Electronic address: stefanie.dedeurwaerdere@uantwerpen.be.
authors: Stefanie
authors: S
authors: Dedeurwaerdere
mesh_terms: D000208:Acute Disease; D000596:Amino Acids; D000818:Animals; D001345:Autoradiography; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D018450:Disease Progression; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D007608:Kainic Acid; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014316:Tritium; D014966:Xanthenes
chemical_list: D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D014316:Tritium; D007608:Kainic Acid
keywords: Autoradiography; Epilepsy; Hippocampal neuropathology; Metabotropic glutamate receptors