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1,25-Dihydroxyvitamin D modulates L-type voltage-gated calcium channels in a subset of neurons in the developing mouse prefrontal cortex.
Gooch, Helen; Cui, Xiaoying; Anggono, Victor; Trzaskowski, Maciej; Tan, Men Chee; Eyles, Darryl W; Burne, Thomas H J; Jang, Se Eun; Mattheisen, Manuel; Hougaard, David M; Pedersen, Bent Nørgaard; Cohen, Arieh; Mortensen, Preben B; Sah, Pankaj; McGrath, John J.
Afiliación
  • Gooch H; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Cui X; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Anggono V; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Trzaskowski M; Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Tan MC; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
  • Eyles DW; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Burne THJ; Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Jang SE; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Mattheisen M; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia.
  • Hougaard DM; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Pedersen BN; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia.
  • Cohen A; Queensland Brain Institute, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Mortensen PB; Clem Jones Centre for Ageing Dementia Research, University of Queensland, St. Lucia, QLD, 4072, Australia.
  • Sah P; Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
  • McGrath JJ; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8000, Aarhus, Denmark.
Transl Psychiatry ; 9(1): 281, 2019 11 11.
Article en En | MEDLINE | ID: mdl-31712549
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Corteza Prefrontal / Señalización del Calcio / Canales de Calcio Tipo L / Neurogénesis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Transl Psychiatry Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Corteza Prefrontal / Señalización del Calcio / Canales de Calcio Tipo L / Neurogénesis Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Transl Psychiatry Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos