Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo

Abstract Astrocytes have been implicated in epileptogenesis and seizure-induced brain injury. Pathological studies reveal a variety of structural abnormalities in astrocytes, such as vacuolization and astrogliosis. While in vivo imaging methods have demonstrated rapid changes in astrocytes under a v...

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Autores principales: Dongjun Guo, Jia Zou, Michael Wong
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:7d3cc6fe42cf4a899be62c4352ace4282021-12-02T12:32:34ZRapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo10.1038/s41598-017-03032-02045-2322https://doaj.org/article/7d3cc6fe42cf4a899be62c4352ace4282017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03032-0https://doaj.org/toc/2045-2322Abstract Astrocytes have been implicated in epileptogenesis and seizure-induced brain injury. Pathological studies reveal a variety of structural abnormalities in astrocytes, such as vacuolization and astrogliosis. While in vivo imaging methods have demonstrated rapid changes in astrocytes under a variety of physiological and pathological conditions, the acute effects of seizures on astrocyte morphology in vivo and corresponding mechanisms of seizure-induced astrocytic injury have not been documented. In this study, we utilized in vivo two-photon imaging to directly monitor the acute structural effects of kainate-induced seizures on cortical astrocytes. Kainate seizures cause an immediate, but transient, vacuolization of astrocytes, followed over several days by astrogliosis. These effects are prevented by pre- or post-treatment with rapamycin, indicating the mTOR pathway is involved in mediating seizure-induced astrocyte injury. These finding have clinical implications for mechanisms of seizure-induced astrocyte injury and potential therapeutic applications with mTOR inhibitors.Dongjun GuoJia ZouMichael WongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dongjun Guo
Jia Zou
Michael Wong
Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
description Abstract Astrocytes have been implicated in epileptogenesis and seizure-induced brain injury. Pathological studies reveal a variety of structural abnormalities in astrocytes, such as vacuolization and astrogliosis. While in vivo imaging methods have demonstrated rapid changes in astrocytes under a variety of physiological and pathological conditions, the acute effects of seizures on astrocyte morphology in vivo and corresponding mechanisms of seizure-induced astrocytic injury have not been documented. In this study, we utilized in vivo two-photon imaging to directly monitor the acute structural effects of kainate-induced seizures on cortical astrocytes. Kainate seizures cause an immediate, but transient, vacuolization of astrocytes, followed over several days by astrogliosis. These effects are prevented by pre- or post-treatment with rapamycin, indicating the mTOR pathway is involved in mediating seizure-induced astrocyte injury. These finding have clinical implications for mechanisms of seizure-induced astrocyte injury and potential therapeutic applications with mTOR inhibitors.
format article
author Dongjun Guo
Jia Zou
Michael Wong
author_facet Dongjun Guo
Jia Zou
Michael Wong
author_sort Dongjun Guo
title Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
title_short Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
title_full Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
title_fullStr Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
title_full_unstemmed Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo
title_sort rapamycin attenuates acute seizure-induced astrocyte injury in mice in vivo
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/7d3cc6fe42cf4a899be62c4352ace428
work_keys_str_mv AT dongjunguo rapamycinattenuatesacuteseizureinducedastrocyteinjuryinmiceinvivo
AT jiazou rapamycinattenuatesacuteseizureinducedastrocyteinjuryinmiceinvivo
AT michaelwong rapamycinattenuatesacuteseizureinducedastrocyteinjuryinmiceinvivo
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