6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c-Fos immunoreactivity throughout the brain

Giulia Albertini, Laura Walrave, Thomas Demuyser, Ann Massie, Dimitri De Bundel, Ilse Smolders

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

© 2017 International League Against Epilepsy. Objective: Besides seizures, patients with epilepsy are affected by a variety of cognitive and psychiatric comorbidities that further impair their quality of life. The present study provides an in-depth characterization of the behavioral alterations induced by 6 Hz corneal kindling. Furthermore, we correlate these behavioral changes to alterations in c-Fos protein expression throughout the brain following kindling. Methods: Adolescent male Naval Medical Research Institute (NMRI) mice were kindled via repetitive subconvulsive 6 Hz corneal stimulations until they reached the fully kindled state (defined as 10 consecutive generalized seizures). Afterwards we performed an elaborate battery of behavioral tests and we evaluated c-Fos expression throughout the brain using immunohistochemistry. Results: Fully kindled mice display an abnormal behavioral phenotype, characterized by basal and amphetamine-induced hyperlocomotion, anhedonia, social withdrawal, and deficits in short- and long-term memory. Moreover, 6 Hz corneal kindling enhances c-Fos immunoreactivity in the visual, parahippocampal, and motor cortices and the limbic system, whereas c-Fos + cells are decreased in the orbital cortex of fully kindled mice. Significance: The behavioral outcomes of 6 Hz corneal kindling cluster into 3 main categories: positive symptoms, negative symptoms, and cognitive impairment. These symptoms are accompanied by c-Fos activation in relevant brain regions once the fully kindled state is established. Based on the face validity of this model, we speculate that 6 Hz corneal kindling can be used to model not only pharmacoresistant limbic seizures, but also several neurobehavioral comorbidities that affect patients with epilepsy.
Original languageEnglish
Pages (from-to)67-78
Number of pages12
JournalEpilepsia
Volume59
Issue number1
Early online date20 Nov 2017
DOIs
Publication statusPublished - Jan 2018

Keywords

  • behavior
  • c-Fos immunoreactivity
  • corneal kindling
  • epilepsy
  • neurobehavioral comorbidities

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