Cargando…

Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABA(A) receptor (GABA(A)R) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABA(A)R activation in neocortical development, including in migratio...

Descripción completa

Detalles Bibliográficos
Autores principales: Furukawa, Tomonori, Yamada, Junko, Akita, Tenpei, Matsushima, Yoshitaka, Yanagawa, Yuchio, Fukuda, Atsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975117/
https://www.ncbi.nlm.nih.gov/pubmed/24734001
http://dx.doi.org/10.3389/fncel.2014.00088
_version_ 1782310088347746304
author Furukawa, Tomonori
Yamada, Junko
Akita, Tenpei
Matsushima, Yoshitaka
Yanagawa, Yuchio
Fukuda, Atsuo
author_facet Furukawa, Tomonori
Yamada, Junko
Akita, Tenpei
Matsushima, Yoshitaka
Yanagawa, Yuchio
Fukuda, Atsuo
author_sort Furukawa, Tomonori
collection PubMed
description γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABA(A) receptor (GABA(A)R) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABA(A)R activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67(GFP/GFP)) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose–response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABA(A)R with the GABA(A)R antagonist SR95531 accelerated radial migration. This effect of GABA(A)R blockade in GAD67(GFP/GFP) mice suggested a role for alternative endogenous GABA(A)R agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABA(A)R. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABA(A)R-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABA(A)R conductance, regulating the radial migration of neurons in the developing neocortex.
format Online
Article
Text
id pubmed-3975117
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-39751172014-04-14 Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex Furukawa, Tomonori Yamada, Junko Akita, Tenpei Matsushima, Yoshitaka Yanagawa, Yuchio Fukuda, Atsuo Front Cell Neurosci Neuroscience γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABA(A) receptor (GABA(A)R) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABA(A)R activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67(GFP/GFP)) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose–response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABA(A)R with the GABA(A)R antagonist SR95531 accelerated radial migration. This effect of GABA(A)R blockade in GAD67(GFP/GFP) mice suggested a role for alternative endogenous GABA(A)R agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABA(A)R. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABA(A)R-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABA(A)R conductance, regulating the radial migration of neurons in the developing neocortex. Frontiers Media S.A. 2014-03-28 /pmc/articles/PMC3975117/ /pubmed/24734001 http://dx.doi.org/10.3389/fncel.2014.00088 Text en Copyright © 2014 Furukawa, Yamada, Akita, Matsushima, Yanagawa and Fukuda. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Furukawa, Tomonori
Yamada, Junko
Akita, Tenpei
Matsushima, Yoshitaka
Yanagawa, Yuchio
Fukuda, Atsuo
Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title_full Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title_fullStr Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title_full_unstemmed Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title_short Roles of taurine-mediated tonic GABA(A) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
title_sort roles of taurine-mediated tonic gaba(a) receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975117/
https://www.ncbi.nlm.nih.gov/pubmed/24734001
http://dx.doi.org/10.3389/fncel.2014.00088
work_keys_str_mv AT furukawatomonori rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex
AT yamadajunko rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex
AT akitatenpei rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex
AT matsushimayoshitaka rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex
AT yanagawayuchio rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex
AT fukudaatsuo rolesoftaurinemediatedtonicgabaareceptoractivationintheradialmigrationofneuronsinthefetalmousecerebralcortex