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Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice
Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of med...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199052/ https://www.ncbi.nlm.nih.gov/pubmed/37208473 http://dx.doi.org/10.1038/s41598-023-35242-0 |
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author | Niitani, Kazuhei Ito, Shiho Wada, Shintaro Izumi, Shoma Nishitani, Naoya Deyama, Satoshi Kaneda, Katsuyuki |
author_facet | Niitani, Kazuhei Ito, Shiho Wada, Shintaro Izumi, Shoma Nishitani, Naoya Deyama, Satoshi Kaneda, Katsuyuki |
author_sort | Niitani, Kazuhei |
collection | PubMed |
description | Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of medial prefrontal cortex (mPFC)-originated seizures. In mPFC slices, whole-cell current-clamp recordings revealed that bath application of picrotoxin induced sporadic epileptiform activities (EAs), which consisted of depolarization with bursts of action potentials in layer 5 pyramidal cells. Addition of NA dramatically shortened the latency and increased the number of EAs. Simultaneous whole-cell and field potential recordings revealed that the EAs are synchronous in the mPFC local circuit. Terazosin, but not atipamezole or timolol, inhibited EA facilitation, indicating the involvement of α(1) adrenoceptors. Intra-mPFC picrotoxin infusion induced seizures in mice in vivo. Addition of NA substantially shortened the seizure latency, while co-infusion of terazosin into the mPFC inhibited the effect of NA. Finally, acute restraint stress shortened the latency of intra-mPFC picrotoxin infusion-induced seizures, whereas prior infusion of terazosin reversed this stress-induced shortening of seizure latency. Our findings suggest that stress facilitates the induction of mPFC-originated seizures via NA stimulation of α(1) adrenoceptors. |
format | Online Article Text |
id | pubmed-10199052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101990522023-05-21 Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice Niitani, Kazuhei Ito, Shiho Wada, Shintaro Izumi, Shoma Nishitani, Naoya Deyama, Satoshi Kaneda, Katsuyuki Sci Rep Article Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of medial prefrontal cortex (mPFC)-originated seizures. In mPFC slices, whole-cell current-clamp recordings revealed that bath application of picrotoxin induced sporadic epileptiform activities (EAs), which consisted of depolarization with bursts of action potentials in layer 5 pyramidal cells. Addition of NA dramatically shortened the latency and increased the number of EAs. Simultaneous whole-cell and field potential recordings revealed that the EAs are synchronous in the mPFC local circuit. Terazosin, but not atipamezole or timolol, inhibited EA facilitation, indicating the involvement of α(1) adrenoceptors. Intra-mPFC picrotoxin infusion induced seizures in mice in vivo. Addition of NA substantially shortened the seizure latency, while co-infusion of terazosin into the mPFC inhibited the effect of NA. Finally, acute restraint stress shortened the latency of intra-mPFC picrotoxin infusion-induced seizures, whereas prior infusion of terazosin reversed this stress-induced shortening of seizure latency. Our findings suggest that stress facilitates the induction of mPFC-originated seizures via NA stimulation of α(1) adrenoceptors. Nature Publishing Group UK 2023-05-19 /pmc/articles/PMC10199052/ /pubmed/37208473 http://dx.doi.org/10.1038/s41598-023-35242-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Niitani, Kazuhei Ito, Shiho Wada, Shintaro Izumi, Shoma Nishitani, Naoya Deyama, Satoshi Kaneda, Katsuyuki Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title | Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title_full | Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title_fullStr | Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title_full_unstemmed | Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title_short | Noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
title_sort | noradrenergic stimulation of α(1) adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199052/ https://www.ncbi.nlm.nih.gov/pubmed/37208473 http://dx.doi.org/10.1038/s41598-023-35242-0 |
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