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@article{5dbe0d26933143c1b519bd914cfdf23f,
title = "6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c-Fos immunoreactivity throughout the brain",
abstract = "{\circledC} 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.",
keywords = "behavior, c-Fos immunoreactivity, corneal kindling, epilepsy, neurobehavioral comorbidities",
author = "Giulia Albertini and Laura Walrave and Thomas Demuyser and Ann Massie and {De Bundel}, Dimitri and Ilse Smolders",
note = "Wiley Periodicals, Inc. {\circledC} 2017 International League Against Epilepsy.",
year = "2018",
month = "1",
doi = "10.1111/epi.13943",
language = "English",
volume = "59",
pages = "67--78",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - 6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c-Fos immunoreactivity throughout the brain

AU - Albertini, Giulia

AU - Walrave, Laura

AU - Demuyser, Thomas

AU - Massie, Ann

AU - De Bundel, Dimitri

AU - Smolders, Ilse

N1 - Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

PY - 2018/1

Y1 - 2018/1

N2 - © 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.

AB - © 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.

KW - behavior

KW - c-Fos immunoreactivity

KW - corneal kindling

KW - epilepsy

KW - neurobehavioral comorbidities

UR - http://www.scopus.com/inward/record.url?scp=85034247956&partnerID=8YFLogxK

U2 - 10.1111/epi.13943

DO - 10.1111/epi.13943

M3 - Article

C2 - 29152735

VL - 59

SP - 67

EP - 78

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 1

ER -

ID: 35770110