6 Hz corneal kindling triggers schizophrenia-like behaviors in fully kindled mice and differential c-fos immunoreactivity in distinct brain regions.
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1
Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry and Drug Analysis, Belgium
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2
University Hospital Brussels, Department of Clinical Biology, Belgium
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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
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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