Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants

Fox, Jordana; Thodeson, Drew Michael; Dolce, Alison

doi:10.1177/0883073820974851

Cited by 14 publications

(3 citation statements)

References 28 publications

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“…A large body of research has shown that mutation of nAChR-related coding genes is relative to the occurrence and development of epilepsy. Changes in the gene coding for nAChRs can lead to changes in nAChR-related structure and function, leading to changes in the local brain potential, resulting in the development of epilepsy [70,71]. When the gene encoding nAChR changes, it may cause changes in nAChR-related structure and function, resulting in changes in brain local potential, resulting in epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the bioactive compounds with efficacy against epilepsy from the herb pairs Polygala tenuifolia - Zizyphus jujuba by modulating CHRNA4/CaMKII signaling pathway: LC-MS/MS combined with network pharmacology analysis and experimental evidence

Nian

Zhao

Wang

et al. 2023

Preprint

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Background Epilepsy is a typical nervous system disorders identified by the spontaneous recurrence of seizures which injure periods of electroencephalographic activity and behavior. Traditional Chinese Medicine (TCM) herb pairs Polygala tenuifolia and Zizyphus jujuba have been used in treatment of epilepsy in China, while the mechanism of action still remains unclear. This article aims to disclose the substances and potential mechanisms of the anti-epilepsy activity of P. tenuifolia and Z. jujuba extract (PZE) using LC-MS/MS, network pharmacology, ethology and molecular biology methods.Methods With the help of the self-built components database, identification of the chemical parameters of PZE was possessed through LC-MS/MS method, and the “ingredient-target-pathway” network of PZE was established through online databeses. Molecular docking was performed using Discovery Studio Visualizer. In the setting of the epilepsy model, pentylenetetrazol (PTZ, 10 mg/kg) was administered intraperitoneally injected for a period of 21 days. Mice were assessed for anxiety-like behavior by Elevated plus maze test, open field test, forced swimming test and tail suspension test. HE staining, western blotting, and immunofluorescence staining were used to detect morphological changes and signal pathway.Results Through network analysis, 37 active ingredients were obtained from PZE, SLC6A4, CHRNA4 and MAOA and were found to play a major role in the PPI network. GO and KEGG analyses that display their anti-epilepsy activity. The"Ingredient-target-pathway"network diagram consists of 99 targets, 24 kinds of constituents, and 20 signaling pathways. The values of M15 and M17 show the largest degree. Molecular docking analysis shows the key components screened by network pharmacology have a good interaction with the predicted targets. Animal experiments results showed that: 1) PZE effectively lengthened the latent time of PTZ-induced epilepsy in mice model. 2) PTZ-induced depression-like behavior was strikingly ameliorated by PZE. 3) Hippocampal neurons are significantly shielded by PZE. 4) PZE was shown to play a key role in modulating the CHRNA4/CaMK II signaling pathway in to show anti-epilepsy potency.Conclusion This study has successfully identified constituents of PZE through LC-MS/MS methods and predicted the potential targets and CHRNA4/CaMK II as potential signaling pathways of anti-epilepsy effects for PZE, which was proved by animal experiments. The results of this paper are conducive to the systematic elucidating of its mechanism of action and the development of TCM-based anti-epilepsy agents.

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Section: Discussionmentioning

confidence: 99%

Characterization of the bioactive compounds with efficacy against epilepsy from the herb pairs Polygala tenuifolia - Zizyphus jujuba by modulating CHRNA4/CaMKII signaling pathway: LC-MS/MS combined with network pharmacology analysis and experimental evidence

Nian

Zhao

Wang

et al. 2023

Preprint

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“…Rats were randomly divided into three groups: control (treated with saline), model group (pilocarpinetreated rats treated with saline) and Cu Zn‐SOD group (pilocarpine‐treated rats treated with viral vector expressing Cu‐Zn‐SOD [ SOD1 ] via the brain cavity). As noted in a previous publication [19], rats were given 200 mg/kg nicotine (Beyotime, Shanghai, China) subcutaneously to combat the surrounding cholinergic effect. After 30 minutes, rats were administrated with pilocarpine hydrochloride (Beyotime)‐to induce epilepsy‐ except for control group, accordingly [20].…”

Section: Methodsmentioning

confidence: 99%

Cu‐Zn SOD suppresses epilepsy in pilocarpine‐treated rats and alters SCN2A/Nrf2/HO‐1 expression

Wen

Tan

Xiang

2022

Epileptic Disorders

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Objective. Copper-zinc superoxide dismutase (Cu-Zn SOD) is downregulated in epilepsy, however, the role of Cu-Zn SOD in epilepsy remains unclear. Methods. Based on the pilocarpine hydrochloride-induced rat model of epilepsy, cortical-striatum brain slices of rats were examined based on field excitatory post-synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH-SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT-PCR and western blot were performed to detect SCN2A/Nrf2/HO-1 gene and protein expression levels, respectively. Results. Cu-Zn SOD over-expression suppressed epilepsy in vivo. In addition, Cu-Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH-SY5Y cells. Moreover, Cu-Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO-1. Lastly, Cu-Zn SOD was shown to modulate the NaV1.2/ Nrf2/HO-1 axis in rats.Significance. In this model, Cu-Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO-1 signalling pathway, indicating that Cu-Zn SOD might be a target for the treatment of epilepsy.

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“…In small clinical studies of patients with ADSHE, nicotine therapy has demonstrated antiseizure effects [21,22].…”

Section: Introduction/rationalementioning

confidence: 99%

How do smoking, vaping, and nicotine affect people with epilepsy and seizures? A scoping review protocol

et al. 2023

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Background Epilepsy is a prevalent disease that requires personalized care to control seizures, reduce side effects, and ameliorate the burden of comorbidities. Smoking is a major cause of preventable death and disease. There is evidence that patients with epilepsy smoke at high rates and that smoking may increase seizure frequency. However, there is a lack systematically synthesized evidence on the interactions between epilepsy and seizures and smoking, tobacco use, vaping, and smoking cessation. Methods and analysis This scoping review protocol guided by the Joanna Briggs Institute Manual for Evidence Synthesis and the PRISMA Extension for Scoping Reviews will investigate what is known about the interactions between smoking and epilepsy. This review will include the population of persons with all types of epilepsy or seizures and examine an inclusive list of concepts including tobacco use, vaping, nicotine replacement, and smoking cessation. The MEDLINE, Embase, APA Psycinfo, CINAHL, Cochrane, Scopus, and Web of Science databases will be searched. Following systematic screening of records, data will be charted, synthesized, and summarized for presentation and publication. Ethics and dissemination No ethical approval is required for this literature-based study. The results of this scoping review will be submitted for publication in a peer-reviewed journal. This synthesis will be informative to clinicians and direct further research that may improve health outcomes for people with epilepsy. Registration This protocol is registered with the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/D3ZK8).

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Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants

Cited by 14 publications

References 28 publications

Characterization of the bioactive compounds with efficacy against epilepsy from the herb pairs Polygala tenuifolia - Zizyphus jujuba by modulating CHRNA4/CaMKII signaling pathway: LC-MS/MS combined with network pharmacology analysis and experimental evidence

Characterization of the bioactive compounds with efficacy against epilepsy from the herb pairs Polygala tenuifolia - Zizyphus jujuba by modulating CHRNA4/CaMKII signaling pathway: LC-MS/MS combined with network pharmacology analysis and experimental evidence

Cu‐Zn SOD suppresses epilepsy in pilocarpine‐treated rats and alters SCN2A/Nrf2/HO‐1 expression

How do smoking, vaping, and nicotine affect people with epilepsy and seizures? A scoping review protocol

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