Department of Economics and Business Economics

1,25-Dihydroxyvitamin D modulates L-type voltage-gated calcium channels in a subset of neurons in the developing mouse prefrontal cortex

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Helen Gooch, Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • ,
  • Xiaoying Cui, Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • ,
  • Victor Anggono, Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • ,
  • Maciej Trzaskowski, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
  • ,
  • Men Chee Tan, Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • ,
  • Darryl W Eyles, The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland 4029, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, Australia; School of Public Health, University of Queensland, Herston, Queensland 4006, Australia; Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA.
  • ,
  • Thomas H J Burne, The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland 4029, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, Australia; School of Public Health, University of Queensland, Herston, Queensland 4006, Australia; Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA.
  • ,
  • Se Eun Jang, Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • ,
  • Manuel Mattheisen
  • David M Hougaard, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
  • ,
  • Bent Nørgaard Pedersen, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
  • ,
  • Arieh Cohen, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
  • ,
  • Preben B Mortensen
  • Pankaj Sah, Brain Research Centre and Department of Biology, Southern University of Science and Technology, Nanshan District, Shenzhen, Guangdong Province, P. R. China.
  • ,
  • John J McGrath

Schizophrenia has been associated with a range of genetic and environmental risk factors. Here we explored a link between two risk factors that converge on a shared neurobiological pathway. Recent genome-wide association studies (GWAS) have identified risk variants in genes that code for L-type voltage-gated calcium channels (L-VGCCs), while epidemiological studies have found an increased risk of schizophrenia in those with neonatal vitamin D deficiency. The active form of vitamin D (1,25(OH)2D) is a secosteroid that rapidly modulates L-VGCCs via non-genomic mechanisms in a range of peripheral tissues, though its non-genomic effects within the brain remain largely unexplored. Here we used calcium imaging, electrophysiology and molecular biology to determine whether 1,25(OH)2D non-genomically modulated L-VGCCs in the developing prefrontal cortex, a region widely implicated in schizophrenia pathophysiology. Wide-field Ca2+ imaging revealed that physiological concentrations of 1,25(OH)2D rapidly enhanced activity-dependent somatic Ca2+ levels in a small subset of neurons in the developing PFC, termed vitamin D-responsive neurons (VDRNs). Somatic nucleated patch recordings revealed a rapid, 1,25(OH)2D-evoked increase in high-voltage-activated (HVA) Ca2+ currents. Enhanced activity-dependent Ca2+ levels were mediated by L-VGCC but not associated with any changes to Cacna1c (L-VGCC pore-forming subunit) mRNA expression. Since L-VGCC activity is critical to healthy neurodevelopment, these data suggest that suboptimal concentrations of 1,25(OH)2D could alter brain maturation through modulation of L-VGCC signalling and as such may provide a parsimonious link between epidemiologic and genetic risk factors for schizophrenia.

Original languageEnglish
Article number281
JournalTranslational Psychiatry
Volume9
Issue1
Number of pages10
ISSN2158-3188
DOIs
Publication statusPublished - 2019

See relations at Aarhus University Citationformats

ID: 171884427