6 Hz corneal kindling triggers schizophrenia-like behaviors in fully kindled mice and differential c-fos immunoreactivity in distinct brain regions.

Abstract

Event Abstract Back to Event 6 Hz corneal kindling triggers schizophrenia-like behaviors in fully kindled mice and differential c-fos immunoreactivity in distinct brain regions. Giulia Albertini1*, Laura Walrave1, Thomas Demuyser2, Dimitri De Bundel1, Ann Massie3 and Ilse J. Smolders1 1 Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry and Drug Analysis, Belgium 2 University Hospital Brussels, Department of Clinical Biology, Belgium 3 Vrije Universiteit Brussel, Department of Pharmaceutical Biotechnology and Molecular Biology, Belgium Epilepsies are a heterogeneous group of neurological disorders characterized by recurrent and spontaneous bursts of neuronal hyperactivity, commonly known as seizures. Together with chronic unpredictable seizures, a variety of comorbidities, such as memory and cognitive dysfunctions and psychiatric symptoms, affects 1 in 2 patients with epilepsy, further deteriorating their quality of life. Experimental models of seizures and epilepsy that mimic neurological and psychiatric comorbidities represent therefore unique tools in epilepsy research. Kindling models are based on the paradigm that repetition of sub-convulsive electrical or chemical stimulations produces a progressive increase in epileptic response, eventually driving bilateral clonic seizures. Due to the clinical phenomenology, pharmacology and focal activation of these seizures which closely reproduce the clinical condition, kindling has been widely used to model chronic induced seizures. Recently the 6 Hz corneal kindling model has been described as a non-invasive, inexpensive and reliable alternative to well-established models of epilepsy. However, due to its novelty, an in-depth characterization of this model has not yet been provided. In this study, after inducing the “fully kindled state” (defined as 10 consecutive generalized seizures) in male NMRI mice via repetitive sub-convulsive corneal stimulations, we performed an elaborate battery of behavioral tests. Besides leading to a decreased seizure threshold, 6 Hz corneal kindling induces an abnormal behavioral phenotype, including hyperactivity, an increased sensitivity to the central nervous system stimulant amphetamine (0.5 mg/Kg), anhedonic-like behavior as well as deficits in short and long term memory. Motivated by these findings, we quantified c-fos+ cells (an early marker of neuronal activation) throughout the brain of corneal kindled and mock-stimulated mice. We show that, besides increasing neuronal activation in limbic regions such as hippocampus, amygdala, cingulate, entorhinal and piriform cortices, 6 Hz corneal kindling also enhances c-fos immunoreactivity in the motor cortex. Moreover, c-fos+ cells are decreased in the orbital cortex of kindled mice, a region involved in social cognition and associated with the negative symptoms of schizophrenia. Overall, we provide evidence that 6 Hz corneal kindling induces schizophrenia-like behavioral changes accompanied by differential activation of relevant brain regions. 6Hz corneal kindling could therefore be used to model epilepsy and schizophrenia comorbidity, known to share a biological basis. Keywords: Epilepsy, Behavior, Schizophrenia, mouse models, 6 Hz corneal kindling, c-Fos immunoreactivity Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Oral Presentation Topic: Cognition and Behavior Citation: Albertini G, Walrave L, Demuyser T, De Bundel D, Massie A and Smolders IJ (2019). 6 Hz corneal kindling triggers schizophrenia-like behaviors in fully kindled mice and differential c-fos immunoreactivity in distinct brain regions.. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00051 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Apr 2017; Published Online: 25 Jan 2019. * Correspondence: Miss. Giulia Albertini, Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry and Drug Analysis, Brussels, 1090, Belgium, galberti@vub.ac.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Giulia Albertini Laura Walrave Thomas Demuyser Dimitri De Bundel Ann Massie Ilse J Smolders Google Giulia Albertini Laura Walrave Thomas Demuyser Dimitri De Bundel Ann Massie Ilse J Smolders Google Scholar Giulia Albertini Laura Walrave Thomas Demuyser Dimitri De Bundel Ann Massie Ilse J Smolders PubMed Giulia Albertini Laura Walrave Thomas Demuyser Dimitri De Bundel Ann Massie Ilse J Smolders Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.