Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy‐prone rat

Cho, Sue J.; Vaca, Michelle A; Miranda, Clive; N’Gouemo, Prosper

doi:10.1111/cns.12770

Cited by 30 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies have also reported the antiepileptic actions of the TRPV1 antagonists. Regarding genetically epilepsy-prone rats ( GEPR-3s ), CPZ (a TRPV1 antagonist) reduced seizure severity in a dose-dependent manner in male rats and in female rats CPZ suppressed seizure susceptibility [ 396 ]. With the application of CPZ and other TRPV1 antagonists such as 5-iodoresiniferatoxin and α-Spinasterol, seizures were suppressed, regardless of the method of induction (4-AP, PTZ, maximal electroshock test, 6 Hz stimulation) [ 392 , 395 , 397 , 398 , 399 , 400 ].…”

Section: Transient Receptor Potential Vanilloid Type 1 (Trpv1)mentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

View full text Add to dashboard Cite

Epilepsy is a chronic brain disease that affects approximately 65 million people worldwide. However, despite the continuous development of antiepileptic drugs, over 30% patients with epilepsy progress to drug-resistant epilepsy. For this reason, it is a high priority objective in preclinical research to find novel therapeutic targets and to develop effective drugs that prevent or reverse the molecular mechanisms underlying epilepsy progression. Among these potential therapeutic targets, we highlight currently available information involving signaling pathways (Wnt/β-catenin, Mammalian Target of Rapamycin (mTOR) signaling and zinc signaling), enzymes (carbonic anhydrase), proteins (erythropoietin, copine 6 and complement system), channels (Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel) and receptors (galanin and melatonin receptors). All of them have demonstrated a certain degree of efficacy not only in controlling seizures but also in displaying neuroprotective activity and in modifying the progression of epilepsy. Although some research with these specific targets has been done in relation with epilepsy, they have not been fully explored as potential therapeutic targets that could help address the unsolved issue of drug-resistant epilepsy and develop new antiseizure therapies for the treatment of epilepsy.

show abstract

Section: Transient Receptor Potential Vanilloid Type 1 (Trpv1)mentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Moreover, CBD anticonvulsant effects are associated with a great variety of mechanisms of action, such as GPR55, TRPV1, 5-HT 1A , BK channels, increased GABAergic neurotransmission, changes in calcium signaling, an indirect modulation of CB1R (Devinsky et al, 2014 ; Britch et al, 2020 ; Lazarini-Lopes et al, 2020b ). In that context, antagonism of TRPV1 receptors suppressed AS in female GEPR-3s and attenuated seizures in male GEPR-3s (Cho et al, 2018 ). Therefore, the exploration of these mechanisms associated with cannabinoids in audiogenic strains is an interesting approach that should be further investigated.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Cannabinoids in Audiogenic Seizures: From Neuronal Networks to Future Perspectives for Epilepsy Treatment

Lazarini-Lopes

Silva

Silva-Júnior

et al. 2021

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Cannabinoids and Cannabis-derived compounds have been receiving especial attention in the epilepsy research scenario. Pharmacological modulation of endocannabinoid system's components, like cannabinoid type 1 receptors (CB1R) and their bindings, are associated with seizures in preclinical models. CB1R expression and functionality were altered in humans and preclinical models of seizures. Additionally, Cannabis-derived compounds, like cannabidiol (CBD), present anticonvulsant activity in humans and in a great variety of animal models. Audiogenic seizures (AS) are induced in genetically susceptible animals by high-intensity sound stimulation. Audiogenic strains, like the Genetically Epilepsy Prone Rats, Wistar Audiogenic Rats, and Krushinsky-Molodkina, are useful tools to study epilepsy. In audiogenic susceptible animals, acute acoustic stimulation induces brainstem-dependent wild running and tonic-clonic seizures. However, during the chronic protocol of AS, the audiogenic kindling (AuK), limbic and cortical structures are recruited, and the initially brainstem-dependent seizures give rise to limbic seizures. The present study reviewed the effects of pharmacological modulation of the endocannabinoid system in audiogenic seizure susceptibility and expression. The effects of Cannabis-derived compounds in audiogenic seizures were also reviewed, with especial attention to CBD. CB1R activation, as well Cannabis-derived compounds, induced anticonvulsant effects against audiogenic seizures, but the effects of cannabinoids modulation and Cannabis-derived compounds still need to be verified in chronic audiogenic seizures. The effects of cannabinoids and Cannabis-derived compounds should be further investigated not only in audiogenic seizures, but also in epilepsy related comorbidities present in audiogenic strains, like anxiety, and depression.

show abstract

“…α -Spinasterol, another TRPV1 antagonist, elevated the seizure threshold in three acute seizure tests in mice [49]. Additionally, inhibition of TRPV1 by capsazepine suppressed seizure susceptibility in the genetically epilepsy-prone rat [50].…”

Section: Trpv1 In the Brainmentioning

confidence: 99%

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

Storozhuk

Moroz

Zholos

2019

BioMed Research International

View full text Add to dashboard Cite

TRPV1 has been originally cloned as the heat and capsaicin receptor implicated in acute pain signalling, while further research has shifted the focus to its importance in chronic pain caused by inflammation and associated with this TRPV1 sensitization. However, accumulating evidence suggests that, apart from pain signalling, TRPV1 subserves many other unrelated to nociception functions in the nervous system. In the brain, TRPV1 can modulate synaptic transmission via both pre- and postsynaptic mechanisms and there is a functional crosstalk between GABA receptors and TRPV1. Other fundamental processes include TRPV1 role in plasticity, microglia-to-neuron communication, and brain development. Moreover, TRPV1 is widely expressed in the peripheral tissues, including the vasculature, gastrointestinal tract, urinary bladder, epithelial cells, and the cells of the immune system. TRPV1 can be activated by a large array of physical (heat, mechanical stimuli) and chemical factors (e.g., protons, capsaicin, resiniferatoxin, and endogenous ligands, such as endovanilloids). This causes two general cell effects, membrane depolarization and calcium influx, thus triggering depending on the cell-type diverse functional responses ranging from neuronal excitation to secretion and smooth muscle contraction. Here, we review recent research on the diverse TRPV1 functions with focus on the brain, vasculature, and some visceral systems as the basis of our better understanding of TRPV1 role in different human disorders.

show abstract

Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy‐prone rat

Abstract: These findings suggest that the TRPV1 channel is a promising molecular target for seizure suppression, with female GEPR-3s exhibiting higher sensitivity than male GEPR-3s.

Cited by 30 publications

References 30 publications

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Cannabinoids in Audiogenic Seizures: From Neuronal Networks to Future Perspectives for Epilepsy Treatment

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

Contact Info

Product

Resources

About