Role of γ-aminobutyric acid in early neuronal development: Studies with an embryonic neuroectodermal stem cell clone

Márta Jelitai, M. Anděrová, K. Markó, K. Kékesi, P. Koncz, E. Syková, E. Madarász

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

γ-Aminobutyric acid (GABA) has been known to function as an autocrine/paracrine signal molecule in addition to its well-known inhibitory neurotransmitter function. Studies on the developing brain and on primary brain cell cultures provided evidence for a variety of GABA functions in periods preceding the formation of synapses. The exact role of GABA in the early neural development, however, is still not well understood. In this study, one-cell-derived NE-4C neuroectodermal stem cells were induced to form neurons and astrocytes in vitro, and the role of GABA was investigated in defined phases of neurogenesis. Noninduced NE-4C cells contained GABA, expressed GABA(A)R α subunits, and carried functional GABA(A) ion channels. A moderate cytoplasmic GABA content was detected during the entire period of differentiation. By the time of the formation of differentiated neurons, neuron-like cells with both high and low GABA content were clearly distinguishable. HPLC analysis indicated that NE-4C cells released GABA into their fluid environment during all stages of neuronal development. By using the patch-clamp technique, GABA-evoked currents were recorded during the entire proliferation/differentiation period, whereas a GABA-evoked increase in intracellular Ca2+ was detected only during the maturation of postmitotic neuronal precursors. Bicuculline blocked both the ion currents and the [Ca2+]i increase in response to GABA. Neuron formation was facilitated by GABA through GABA(A) ion channels during postmitotic differentiation, but not earlier during the phases of cell fate commitment. Although the data clearly demonstrate an early responsiveness to GABA, understanding the significance of GABA influence in early neural cell fate decisions will require further investigation.

Original languageEnglish
Pages (from-to)801-811
Number of pages11
JournalJournal of Neuroscience Research
Volume76
Issue number6
DOIs
Publication statusPublished - Jun 15 2004

Fingerprint

Aminobutyrates
Embryonic Stem Cells
gamma-Aminobutyric Acid
Clone Cells
Neurons
Ion Channels
Primary Cell Culture
Bicuculline

Keywords

  • Calcium response
  • GABA-evoked current
  • Neural stem cell
  • Neuronal development
  • Nonsynaptic GABA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of γ-aminobutyric acid in early neuronal development : Studies with an embryonic neuroectodermal stem cell clone. / Jelitai, Márta; Anděrová, M.; Markó, K.; Kékesi, K.; Koncz, P.; Syková, E.; Madarász, E.

In: Journal of Neuroscience Research, Vol. 76, No. 6, 15.06.2004, p. 801-811.

Research output: Contribution to journalArticle

@article{3c2aebd6057c4f2d98e89ed5192df704,
title = "Role of γ-aminobutyric acid in early neuronal development: Studies with an embryonic neuroectodermal stem cell clone",
abstract = "γ-Aminobutyric acid (GABA) has been known to function as an autocrine/paracrine signal molecule in addition to its well-known inhibitory neurotransmitter function. Studies on the developing brain and on primary brain cell cultures provided evidence for a variety of GABA functions in periods preceding the formation of synapses. The exact role of GABA in the early neural development, however, is still not well understood. In this study, one-cell-derived NE-4C neuroectodermal stem cells were induced to form neurons and astrocytes in vitro, and the role of GABA was investigated in defined phases of neurogenesis. Noninduced NE-4C cells contained GABA, expressed GABA(A)R α subunits, and carried functional GABA(A) ion channels. A moderate cytoplasmic GABA content was detected during the entire period of differentiation. By the time of the formation of differentiated neurons, neuron-like cells with both high and low GABA content were clearly distinguishable. HPLC analysis indicated that NE-4C cells released GABA into their fluid environment during all stages of neuronal development. By using the patch-clamp technique, GABA-evoked currents were recorded during the entire proliferation/differentiation period, whereas a GABA-evoked increase in intracellular Ca2+ was detected only during the maturation of postmitotic neuronal precursors. Bicuculline blocked both the ion currents and the [Ca2+]i increase in response to GABA. Neuron formation was facilitated by GABA through GABA(A) ion channels during postmitotic differentiation, but not earlier during the phases of cell fate commitment. Although the data clearly demonstrate an early responsiveness to GABA, understanding the significance of GABA influence in early neural cell fate decisions will require further investigation.",
keywords = "Calcium response, GABA-evoked current, Neural stem cell, Neuronal development, Nonsynaptic GABA",
author = "M{\'a}rta Jelitai and M. Anděrov{\'a} and K. Mark{\'o} and K. K{\'e}kesi and P. Koncz and E. Sykov{\'a} and E. Madar{\'a}sz",
year = "2004",
month = "6",
day = "15",
doi = "10.1002/jnr.20106",
language = "English",
volume = "76",
pages = "801--811",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Role of γ-aminobutyric acid in early neuronal development

T2 - Studies with an embryonic neuroectodermal stem cell clone

AU - Jelitai, Márta

AU - Anděrová, M.

AU - Markó, K.

AU - Kékesi, K.

AU - Koncz, P.

AU - Syková, E.

AU - Madarász, E.

PY - 2004/6/15

Y1 - 2004/6/15

N2 - γ-Aminobutyric acid (GABA) has been known to function as an autocrine/paracrine signal molecule in addition to its well-known inhibitory neurotransmitter function. Studies on the developing brain and on primary brain cell cultures provided evidence for a variety of GABA functions in periods preceding the formation of synapses. The exact role of GABA in the early neural development, however, is still not well understood. In this study, one-cell-derived NE-4C neuroectodermal stem cells were induced to form neurons and astrocytes in vitro, and the role of GABA was investigated in defined phases of neurogenesis. Noninduced NE-4C cells contained GABA, expressed GABA(A)R α subunits, and carried functional GABA(A) ion channels. A moderate cytoplasmic GABA content was detected during the entire period of differentiation. By the time of the formation of differentiated neurons, neuron-like cells with both high and low GABA content were clearly distinguishable. HPLC analysis indicated that NE-4C cells released GABA into their fluid environment during all stages of neuronal development. By using the patch-clamp technique, GABA-evoked currents were recorded during the entire proliferation/differentiation period, whereas a GABA-evoked increase in intracellular Ca2+ was detected only during the maturation of postmitotic neuronal precursors. Bicuculline blocked both the ion currents and the [Ca2+]i increase in response to GABA. Neuron formation was facilitated by GABA through GABA(A) ion channels during postmitotic differentiation, but not earlier during the phases of cell fate commitment. Although the data clearly demonstrate an early responsiveness to GABA, understanding the significance of GABA influence in early neural cell fate decisions will require further investigation.

AB - γ-Aminobutyric acid (GABA) has been known to function as an autocrine/paracrine signal molecule in addition to its well-known inhibitory neurotransmitter function. Studies on the developing brain and on primary brain cell cultures provided evidence for a variety of GABA functions in periods preceding the formation of synapses. The exact role of GABA in the early neural development, however, is still not well understood. In this study, one-cell-derived NE-4C neuroectodermal stem cells were induced to form neurons and astrocytes in vitro, and the role of GABA was investigated in defined phases of neurogenesis. Noninduced NE-4C cells contained GABA, expressed GABA(A)R α subunits, and carried functional GABA(A) ion channels. A moderate cytoplasmic GABA content was detected during the entire period of differentiation. By the time of the formation of differentiated neurons, neuron-like cells with both high and low GABA content were clearly distinguishable. HPLC analysis indicated that NE-4C cells released GABA into their fluid environment during all stages of neuronal development. By using the patch-clamp technique, GABA-evoked currents were recorded during the entire proliferation/differentiation period, whereas a GABA-evoked increase in intracellular Ca2+ was detected only during the maturation of postmitotic neuronal precursors. Bicuculline blocked both the ion currents and the [Ca2+]i increase in response to GABA. Neuron formation was facilitated by GABA through GABA(A) ion channels during postmitotic differentiation, but not earlier during the phases of cell fate commitment. Although the data clearly demonstrate an early responsiveness to GABA, understanding the significance of GABA influence in early neural cell fate decisions will require further investigation.

KW - Calcium response

KW - GABA-evoked current

KW - Neural stem cell

KW - Neuronal development

KW - Nonsynaptic GABA

UR - http://www.scopus.com/inward/record.url?scp=2642562130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642562130&partnerID=8YFLogxK

U2 - 10.1002/jnr.20106

DO - 10.1002/jnr.20106

M3 - Article

C2 - 15160392

AN - SCOPUS:2642562130

VL - 76

SP - 801

EP - 811

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 6

ER -