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Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder
Interneurons are fundamental cells for maintaining the excitation-inhibition balance in the brain in health and disease. While interneurons have been shown to play a key role in the pathophysiology of autism spectrum disorder (ASD) in adult mice, little is known about how their maturation is altered...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930104/ https://www.ncbi.nlm.nih.gov/pubmed/36819097 http://dx.doi.org/10.3389/fcell.2023.1112062 |
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author | Ahmed, Noorya Yasmin Knowles, Rhys Liu, Lixinyu Yan, Yiming Li, Xiaohan Schumann, Ulrike Wang, Yumeng Sontani, Yovina Reynolds, Nathan Natoli, Riccardo Wen, Jiayu Del Pino, Isabel Mi, Da Dehorter, Nathalie |
author_facet | Ahmed, Noorya Yasmin Knowles, Rhys Liu, Lixinyu Yan, Yiming Li, Xiaohan Schumann, Ulrike Wang, Yumeng Sontani, Yovina Reynolds, Nathan Natoli, Riccardo Wen, Jiayu Del Pino, Isabel Mi, Da Dehorter, Nathalie |
author_sort | Ahmed, Noorya Yasmin |
collection | PubMed |
description | Interneurons are fundamental cells for maintaining the excitation-inhibition balance in the brain in health and disease. While interneurons have been shown to play a key role in the pathophysiology of autism spectrum disorder (ASD) in adult mice, little is known about how their maturation is altered in the developing striatum in ASD. Here, we aimed to track striatal developing interneurons and elucidate the molecular and physiological alterations in the Cntnap2 knockout mouse model. Using Stereo-seq and single-cell RNA sequencing data, we first characterized the pattern of expression of Cntnap2 in the adult brain and at embryonic stages in the medial ganglionic eminence (MGE), a transitory structure producing most cortical and striatal interneurons. We found that Cntnap2 is enriched in the striatum, compared to the cortex, particularly in the developing striatal cholinergic interneurons. We then revealed enhanced MGE-derived cell proliferation, followed by increased cell loss during the canonical window of developmental cell death in the Cntnap2 knockout mice. We uncovered specific cellular and molecular alterations in the developing Lhx6-expressing cholinergic interneurons of the striatum, which impacts interneuron firing properties during the first postnatal week. Overall, our work unveils some of the mechanisms underlying the shift in the developmental trajectory of striatal interneurons which greatly contribute to the ASD pathogenesis. |
format | Online Article Text |
id | pubmed-9930104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99301042023-02-16 Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder Ahmed, Noorya Yasmin Knowles, Rhys Liu, Lixinyu Yan, Yiming Li, Xiaohan Schumann, Ulrike Wang, Yumeng Sontani, Yovina Reynolds, Nathan Natoli, Riccardo Wen, Jiayu Del Pino, Isabel Mi, Da Dehorter, Nathalie Front Cell Dev Biol Cell and Developmental Biology Interneurons are fundamental cells for maintaining the excitation-inhibition balance in the brain in health and disease. While interneurons have been shown to play a key role in the pathophysiology of autism spectrum disorder (ASD) in adult mice, little is known about how their maturation is altered in the developing striatum in ASD. Here, we aimed to track striatal developing interneurons and elucidate the molecular and physiological alterations in the Cntnap2 knockout mouse model. Using Stereo-seq and single-cell RNA sequencing data, we first characterized the pattern of expression of Cntnap2 in the adult brain and at embryonic stages in the medial ganglionic eminence (MGE), a transitory structure producing most cortical and striatal interneurons. We found that Cntnap2 is enriched in the striatum, compared to the cortex, particularly in the developing striatal cholinergic interneurons. We then revealed enhanced MGE-derived cell proliferation, followed by increased cell loss during the canonical window of developmental cell death in the Cntnap2 knockout mice. We uncovered specific cellular and molecular alterations in the developing Lhx6-expressing cholinergic interneurons of the striatum, which impacts interneuron firing properties during the first postnatal week. Overall, our work unveils some of the mechanisms underlying the shift in the developmental trajectory of striatal interneurons which greatly contribute to the ASD pathogenesis. Frontiers Media S.A. 2023-02-01 /pmc/articles/PMC9930104/ /pubmed/36819097 http://dx.doi.org/10.3389/fcell.2023.1112062 Text en Copyright © 2023 Ahmed, Knowles, Liu, Yan, Li, Schumann, Wang, Sontani, Reynolds, Natoli, Wen, Del Pino, Mi and Dehorter. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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 | Cell and Developmental Biology Ahmed, Noorya Yasmin Knowles, Rhys Liu, Lixinyu Yan, Yiming Li, Xiaohan Schumann, Ulrike Wang, Yumeng Sontani, Yovina Reynolds, Nathan Natoli, Riccardo Wen, Jiayu Del Pino, Isabel Mi, Da Dehorter, Nathalie Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title | Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title_full | Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title_fullStr | Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title_full_unstemmed | Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title_short | Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder |
title_sort | developmental deficits of mge-derived interneurons in the cntnap2 knockout mouse model of autism spectrum disorder |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930104/ https://www.ncbi.nlm.nih.gov/pubmed/36819097 http://dx.doi.org/10.3389/fcell.2023.1112062 |
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