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Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro

Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcriptio...

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Autores principales: Turovsky, Egor A., Turovskaya, Maria V., Fedotova, Evgeniya I., Babaev, Alexey A., Tarabykin, Victor S., Varlamova, Elena G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198236/
https://www.ncbi.nlm.nih.gov/pubmed/34073140
http://dx.doi.org/10.3390/ijms22115968
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author Turovsky, Egor A.
Turovskaya, Maria V.
Fedotova, Evgeniya I.
Babaev, Alexey A.
Tarabykin, Victor S.
Varlamova, Elena G.
author_facet Turovsky, Egor A.
Turovskaya, Maria V.
Fedotova, Evgeniya I.
Babaev, Alexey A.
Tarabykin, Victor S.
Varlamova, Elena G.
author_sort Turovsky, Egor A.
collection PubMed
description Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcription factors remain poorly understood. In this study, we have shown that transcription factors Satb1 and Satb2 participate in the regulation of genes encoding the NMDA-, AMPA-, and KA- receptor subunits and the inhibitory GABA(A) receptor. Deletion of gene for either Satb1 or Satb2 homologous factors induces the expression of genes encoding the NMDA receptor subunits, thereby leading to higher amplitudes of Ca(2+)-signals in neurons derived from the Satb1-deficient (Satb1(fl/+) * Nex(Cre/+)) and Satb1-null mice (Satb1(fl/fl) * Nex(Cre/+)) in response to the selective agonist reducing the EC50 for the NMDA receptor. Simultaneously, there is an increase in the expression of the Gria2 gene, encoding the AMPA receptor subunit, thus decreasing the Ca(2+)-signals of neurons in response to the treatment with a selective agonist (5-Fluorowillardiine (FW)). The Satb1 deletion increases the sensitivity of the KA receptor to the agonist (domoic acid), in the cortical neurons of the Satb1-deficient mice but decreases it in the Satb1-null mice. At the same time, the Satb2 deletion decreases Ca(2+)-signals and the sensitivity of the KA receptor to the agonist in neurons from the Satb1-null and the Satb1-deficient mice. The Satb1 deletion affects the development of the inhibitory system of neurotransmission resulting in the suppression of the neuron maturation process and switching the GABAergic responses from excitatory to inhibitory, while the Satb2 deletion has a similar effect only in the Satb1-null mice. We show that the Satb1 and Satb2 transcription factors are involved in the regulation of the transmission of excitatory signals and inhibition of the neuronal network in the cortical cell culture.
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spelling pubmed-81982362021-06-14 Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro Turovsky, Egor A. Turovskaya, Maria V. Fedotova, Evgeniya I. Babaev, Alexey A. Tarabykin, Victor S. Varlamova, Elena G. Int J Mol Sci Article Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcription factors remain poorly understood. In this study, we have shown that transcription factors Satb1 and Satb2 participate in the regulation of genes encoding the NMDA-, AMPA-, and KA- receptor subunits and the inhibitory GABA(A) receptor. Deletion of gene for either Satb1 or Satb2 homologous factors induces the expression of genes encoding the NMDA receptor subunits, thereby leading to higher amplitudes of Ca(2+)-signals in neurons derived from the Satb1-deficient (Satb1(fl/+) * Nex(Cre/+)) and Satb1-null mice (Satb1(fl/fl) * Nex(Cre/+)) in response to the selective agonist reducing the EC50 for the NMDA receptor. Simultaneously, there is an increase in the expression of the Gria2 gene, encoding the AMPA receptor subunit, thus decreasing the Ca(2+)-signals of neurons in response to the treatment with a selective agonist (5-Fluorowillardiine (FW)). The Satb1 deletion increases the sensitivity of the KA receptor to the agonist (domoic acid), in the cortical neurons of the Satb1-deficient mice but decreases it in the Satb1-null mice. At the same time, the Satb2 deletion decreases Ca(2+)-signals and the sensitivity of the KA receptor to the agonist in neurons from the Satb1-null and the Satb1-deficient mice. The Satb1 deletion affects the development of the inhibitory system of neurotransmission resulting in the suppression of the neuron maturation process and switching the GABAergic responses from excitatory to inhibitory, while the Satb2 deletion has a similar effect only in the Satb1-null mice. We show that the Satb1 and Satb2 transcription factors are involved in the regulation of the transmission of excitatory signals and inhibition of the neuronal network in the cortical cell culture. MDPI 2021-05-31 /pmc/articles/PMC8198236/ /pubmed/34073140 http://dx.doi.org/10.3390/ijms22115968 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Turovsky, Egor A.
Turovskaya, Maria V.
Fedotova, Evgeniya I.
Babaev, Alexey A.
Tarabykin, Victor S.
Varlamova, Elena G.
Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title_full Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title_fullStr Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title_full_unstemmed Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title_short Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca(2+) Signaling in the Cortical Neurons In Vitro
title_sort role of satb1 and satb2 transcription factors in the glutamate receptors expression and ca(2+) signaling in the cortical neurons in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198236/
https://www.ncbi.nlm.nih.gov/pubmed/34073140
http://dx.doi.org/10.3390/ijms22115968
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