TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo

Abstract: Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+ . Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but the...

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Autores principales: Belkacemi, Thabet, Niermann, Alexander, Hofmann, Laura, Wissenbach, Ulrich, Birnbaumer, Lutz, Leidinger, Petra, Backes, Christina, Meese, Eckart, Keller, Andreas, Bai, Xianshu, Scheller, Anja, Kirchhoff, Frank, Philipp, Stephan E., Weissgerber, Petra, Flockerzi, Veit, Beck, Andreas
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley 2019
Materias:
TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8724
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8724
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
spellingShingle TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
topic_facet TEJIDO NERVIOSO
CELULAS
CEREBRO
CORTEZA CEREBRAL
HERIDAS
description Abstract: Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+ . Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
format Artículo
author Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author_facet Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author_sort Belkacemi, Thabet
title TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_short TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_fullStr TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full_unstemmed TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_sort trpc1- and trpc3-dependent ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
publisher Wiley
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8724
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