Increased TRPV1 Channels and FosB Protein Expression Are Associated with Chronic Epileptic Seizures and Anxiogenic-like Behaviors in a Preclinical Model of Temporal Lobe Epilepsy.

Willian Lazarini-Lopes,Christie Ramos Andrade Leite-Panissi,Norberto Garcia-Cairasco,Gleice Kelli Silva-Cardoso

doi:10.3390/biomedicines10020416

Willian Lazarini-Lopes, Christie Ramos Andrade Leite-Panissi + Show 2 more

Open Access

https://doi.org/10.3390/biomedicines10020416

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Journal: Biomedicines	Publication Date: Feb 10, 2022
Citations: 11	License type: CC BY 4.0

Affiliation: Universidade de São Paulo

Abstract

Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic epileptic seizures in anxiety-like behavior and TRPV1 channels expression in a genetic model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. WARs were submitted to audiogenic kindling (AK), a preclinical model of temporal lobe epilepsy (TLE) and behavioral tests were performed in the open-field (OF), and light-dark box (LDB) tests 24 h after AK. WARs displayed increased anxiety-like behavior and TRPV1R expression in the hippocampal CA1 area and basolateral amygdala nucleus (BLA) when compared to control Wistar rats. Chronic seizures increased anxiety-like behaviors and TRPV1 and FosB expression in limbic and brainstem structures involved with epilepsy and anxiety comorbidity, such as the hippocampus, superior colliculus, and periaqueductal gray matter. Therefore, these results highlight previously unrecognized alterations in TRPV1 expression in brain structures involved with TLE and anxiogenic-like behaviors in a genetic model of epilepsy, the WAR strain, supporting an important role of TRPV1 in the modulation of neurological disorders and associated neuropsychiatric comorbidities.

Highlights

Epilepsies are neurological disorders characterized by chronic epileptic seizures and their consequent neuropsychiatric comorbidities [1,2]
In the beginning of the protocol, Wistar Audiogenic Rat (WAR) developed brainstem audiogenic seizures (AGS) in response to intense sound stimulation; seizures were characterized by wild running with jumps and atonic falls followed by generalized tonic-clonic seizure behaviors, such as forelimb hyperextension, partial or generalized clonic seizures
During audiogenic kindling (AK), limbic seizures coexist with those that originated from brainstem structures; this phenomenon is illustrated by the appearance of novel clonic seizure behaviors such as those described by Racine [49], similar to facial and forelimb myoclonus, followed by body elevation and fall (Figure 2)

Summary

Introduction

Epilepsies are neurological disorders characterized by chronic epileptic seizures and their consequent neuropsychiatric comorbidities [1,2]. We can highlight anxiety, which is one of the most common comorbidities associated with epilepsies, because of the epileptogenic processes and as a cause of its exacerbation, which indicates a bidirectional relationship between epilepsies and anxiety [3,4,5]. The phenomenon of the bidirectionality between neurological disorders and neuropsychiatric comorbidities has been frequently discussed in the literature [10,11]. Studies demonstrated that seizure severity is highly correlated with anxiety and other neuropsychiatric comorbidities, such as depression, in patients with epilepsies, supporting a direct

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