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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.
Afiliación
  • Ahmed NY; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Knowles R; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Liu L; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Yan Y; Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China.
  • Li X; Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China.
  • Schumann U; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Wang Y; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Sontani Y; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Reynolds N; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Natoli R; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Wen J; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
  • Del Pino I; Institute of Neurosciences, Spanish National Research Council (CSIC), Sant Joan d'Alacant, Spain.
  • Mi D; Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing, China.
  • Dehorter N; The Australian National University, The John Curtin School of Medical Research, Canberra, ACT, Australia.
Front Cell Dev Biol ; 11: 1112062, 2023.
Article en En | MEDLINE | ID: mdl-36819097
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cell Dev Biol Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cell Dev Biol Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza