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Cited by 34Ion channel regulation and functionNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

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

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Smedler, Erik, Louhivuori, Lauri, Romanov, Roman A., Masini, Débora, Dehnisch Ellström, Ivar, Wang, Chungliang, Caramia, Martino, West, Zoe +8 more·2022·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2108768119PMC PMC8851547
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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.

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  • Embryonic deletion of CaV1.2 in cortical neurons disturbs spontaneous calcium activity, causing increased anxiety in mice.

    “embryonic deletion of CaV1.2 in cortical neurons disturbs spontaneous calcium activity, causing increased anxiety in mice96”

    From CYFIP1 governs the development of cortical axons by modulating calcium availability (2025) · cites this paper as [96]

    The Discussion (page unavailable) reports that forebrain-specific Cacna1c knockout mice had altered spontaneous calcium activity in the developing neocortex and increased anxiety-like behavior as adults. The Methods identify an Emx1-Cre forebrain-specific manipulation, while the Results measure calcium activity in neural progenitors at postnatal day 7. The copy therefore supports the central finding but not the claim’s more specific description of an embryonic deletion in cortical neurons. (LLM, conf=0.85)

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Authors
Smedler, E., Louhivuori, L., Romanov, R. A., Masini, D., Dehnisch Ellström, I., Wang, C., Caramia, M., West, Z., Zhang, S., Rebellato, P., Malmersjö, S., Brusini, I., Kanatani, S., Fisone, G., Harkany, T., & Uhlén, P.
Affiliations
  • Karolinska Institutet (SE)
  • Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-17177, Sweden
  • KTH Royal Institute of Technology (SE)
Corresponding author
  • Smedler, Erik
  • Uhlén, Per
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2022-02-08
Volume
119
Issue
7
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2108768119
PMC
PMC8851547
OpenAlex
W4210898293
Cited by
34
References
67
Citations by year
2026: 4 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 4
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Vetenskapsrådet (2013-3189, 2017-00815, 2021-03108)
  • Hjärnfonden (FO2017-0107, FO2018-0209, FO2020-0199)
  • Cancerfonden (CAN 2016-801, 19 0544 Pj, 19 0545 Us)
  • Barncancerfonden (PR2018-0123, PR2020-0124)
  • European Molecular Biology Organization (ALTF 596-2014)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
CACNA1C, L-type calcium channels, spontaneous calcium activity, neural progenitor cells, brain development, anxiety, gene deletion, schizophrenia, bipolar disorder
MeSH terms
Animals, Anxiety Disorders, Biological Clocks, Brain, Calcium, Mice, Knockout, Gene Expression Regulation, Developmental, Genetic Predisposition to Disease, Calcium Channels, L-Type, Mice, Neural Stem Cells

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