Disrupted <i>Cacna1c</i> gene expression perturbs spontaneous Ca <sup>2+</sup> activity causing abnormal brain development and increased anxiety-Reference-Cited by-同舟云学术

Disrupted Cacna1c gene expression perturbs spontaneous Ca ²⁺ activity causing abnormal brain development and increased anxiety

Published:2022-02-08 Issue:7 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Smedler Erik¹²,Louhivuori Lauri¹,Romanov Roman A.³⁴,Masini Débora³^ORCID,Dehnisch Ellström Ivar¹^ORCID,Wang Chungliang⁵,Caramia Martino³,West Zoe¹,Zhang Songbai¹^ORCID,Rebellato Paola¹,Malmersjö Seth¹^ORCID,Brusini Irene⁵⁶^ORCID,Kanatani Shigeaki¹,Fisone Gilberto³^ORCID,Harkany Tibor³⁴^ORCID,Uhlén Per¹^ORCID

Affiliation:

1. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-17177, Sweden

2. Department of Neuroscience and Physiology, Gothenburg University, Gothenburg SE-41345, Sweden

3. Department of Neuroscience, Karolinska Institutet, Stockholm SE-17177, Sweden

4. Department of Molecular Neurosciences, Centre for Brain Research, Medical University of Vienna, Vienna A-1090, Austria

5. Department of Biomedical Engineering and Health Systems, KTH Royal Institute of Technology, Huddinge SE-14152, Sweden

6. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge SE-14183, Sweden

Abstract

Significance The gene CACNA1C encodes for a calcium channel that has been linked to various psychiatric conditions, including schizophrenia and bipolar disorder, through hitherto unknown cellular mechanisms. Here, we report that deletion of Cacna1c in neurons of the developing brain disrupts spontaneous calcium activity and causes abnormal brain development and anxiety. Our results indicate that marginally alterations in the expression level of Cacna1c have major effects on the intrinsic spontaneous calcium activity of neural progenitors that play a crucial role in brain development. Thus, Cacna1c acts as a molecular switch that can increase susceptibility to psychiatric disease.

Funder

Vetenskapsrådet

Hjärnfonden

Cancerfonden

Barncancerfonden

European Molecular Biology Organization

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2108768119