Work

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

Year: 2022

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2108768119

Authors: Erik Smedler, Lauri Louhivuori, Roman A. Romanov, Débora Masini, Ivar Dehnisch Ellström, Chungliang Wang, Martino Caramia, Zoe West, Songbai Zhang, Paola Rebellato, Seth Malmersjö, Irene Brusini, Shigeaki Kanatani, Gilberto Fisone, Tibor Harkany, Per Uhlén

Institutions: Karolinska Institutet, University of Gothenburg, Medical University of Vienna, KTH Royal Institute of Technology

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: European Molecular Biology Organization, Cancerfonden, Hjärnfonden, Vetenskapsrådet, Barncancerfonden, Novo Nordisk Fonden

Awards: G1297281994, Förbättrad diagnos av lymfom med 3D-mikroskopi, G1385202384, G1921872705, G2264001453, G3231881271, Role of Calcium Signaling in Regulating Cell Division in the Embryonic Brain, Förbättrad diagnostisering av lymfom hos barn med 3D-mikroskopi, G4975246203, G5459092916, G5655107736, G6370977435, G7516226887, Exploration of Intratumoral Heterogeneity with Multimodal 3D Imaging at Single-Cell Resolution to Improve Precision Medicine for Cancer, Role of Impaired Spontaneous Calcium Activity in the Embryonic Brain For Neuropsychiatric Disorders, G8760209226

OpenAlex ID: W4210898293

FWCI: 2.026

Cites: 67

Cited by: 31

Related to: 10