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

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.

Cannabidiol attenuates seizure susceptibility and behavioural deficits in adult CDKL5R59X knock‐in mice

“…Cannabidiol is a potent and selective agonist of the Ca 2+ permeable TRPV1 channel, which is also involved in the modulation of synaptic glutamate release (Bisogno et al, 2001; Musella et al, 2009). Here, we found increased cortical expression of TRPV1 in adult R59X mice, consistent with the fact that the expression of TRPV1 is increased in preclinical models and patients with temporal lobe epilepsy, tuberous sclerosis complex and focal cortical dysplasia type IIb (Lazarini‐Lopes et al, 2022; Shu et al, 2013; Sun et al, 2013). TRPV1 antagonists can protect against seizures (Cho et al, 2018; Gonzalez‐Reyes et al, 2013; Shirazi et al, 2014), and although cannabidiol is a TRPV1 agonist, it rapidly desensitizes the channel, which may contribute to its antiseizure activity (Bisogno et al, 2001; de Petrocellis et al, 2011; Gray et al, 2020; Iannotti et al, 2014; Vilela et al, 2017).…”

New Insights into the Mutual Promotion of Rosacea, Anxiety, and Depression from Neuroendocrine Immune Aspects

“…This result may be due to changes in 5-hydroxytryptamine (5-HT)1A, GABAA, and NMDA receptor expression, which can be prevented by antidepressant drugs. 33 However, the mechanism by which TRPV1 aggregation regulates the whole process remains unclear, and TRPV1 is associated with other neurotransmitter systems associated with neuropsychiatric disorders, especially endogenous cannabinoids, 34 which makes its neurobiological function more challenging to understand. Moreover, TRPV4 is likewise abundantly expressed in astrocytes.…”

Neuroprotective potential of Moringa oleifera mediated by NF‐kB/Nrf2/HO‐1 signaling pathway: A review

“…Epilepsy is a neurological condition characterized by excessive neuronal firing and recurrent seizure events (Lazarini‐Lopes et al, 2022). Methanolic and ethanolic extract of moringa leaves delayed the onset of pentylenetetrazol (PTZ)‐induced seizures and maximal electroshock (MES)‐induced convulsions, and there was a substantial reduction in the duration of hind limb extension, exhibiting potent anticonvulsant activity (Paikra, 2017).…”

“…Epilepsy is a neurological condition characterized by excessive neuronal firing and recurrent seizure events (Lazarini-Lopes et al, 2022).…”