Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression

The ATP1A2 coding α2 subunit of Na,K‐ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2tmCKwk/+) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and head...

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Main Authors: Hiroki Sugimoto, Masaaki Sato, Junichi Nakai, Kiyoshi Kawakami
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12848
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author Hiroki Sugimoto
Masaaki Sato
Junichi Nakai
Kiyoshi Kawakami
author_facet Hiroki Sugimoto
Masaaki Sato
Junichi Nakai
Kiyoshi Kawakami
author_sort Hiroki Sugimoto
collection DOAJ
description The ATP1A2 coding α2 subunit of Na,K‐ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2tmCKwk/+) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2tmCKwk/+ crossed with transgenic mice expressing G‐CaMP7 in cortical neurons and astrocytes (Atp1a2+/−), we analyzed the changes in Ca2+ concentrations during CSD. The propagation speed of Ca2+ waves and the percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/− were higher than those in wild‐type mice. Increased percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/− may contribute to FHM2 pathophysiology.
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spelling doaj.art-3ffa051a7ab94110b181a16f7dd728302022-12-21T17:48:38ZengWileyFEBS Open Bio2211-54632020-06-011061031104310.1002/2211-5463.12848Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depressionHiroki Sugimoto0Masaaki Sato1Junichi Nakai2Kiyoshi Kawakami3Division of Biology Center for Molecular Medicine Jichi Medical University Tochigi JapanGraduate School of Science and Engineering Saitama University JapanGraduate School of Science and Engineering Saitama University JapanDivision of Biology Center for Molecular Medicine Jichi Medical University Tochigi JapanThe ATP1A2 coding α2 subunit of Na,K‐ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2tmCKwk/+) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2tmCKwk/+ crossed with transgenic mice expressing G‐CaMP7 in cortical neurons and astrocytes (Atp1a2+/−), we analyzed the changes in Ca2+ concentrations during CSD. The propagation speed of Ca2+ waves and the percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/− were higher than those in wild‐type mice. Increased percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/− may contribute to FHM2 pathophysiology.https://doi.org/10.1002/2211-5463.12848astrocyteAtp1a2calcium imagingCSDFHM2G‐CaMP7
spellingShingle Hiroki Sugimoto
Masaaki Sato
Junichi Nakai
Kiyoshi Kawakami
Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
FEBS Open Bio
astrocyte
Atp1a2
calcium imaging
CSD
FHM2
G‐CaMP7
title Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
title_full Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
title_fullStr Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
title_full_unstemmed Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
title_short Astrocytes in Atp1a2‐deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
title_sort astrocytes in atp1a2 deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression
topic astrocyte
Atp1a2
calcium imaging
CSD
FHM2
G‐CaMP7
url https://doi.org/10.1002/2211-5463.12848
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AT masaakisato astrocytesinatp1a2deficientheterozygousmiceexhibithyperactivityafterinductionofcorticalspreadingdepression
AT junichinakai astrocytesinatp1a2deficientheterozygousmiceexhibithyperactivityafterinductionofcorticalspreadingdepression
AT kiyoshikawakami astrocytesinatp1a2deficientheterozygousmiceexhibithyperactivityafterinductionofcorticalspreadingdepression