Voltage gated calcium channels and vitamin D: exploring the convergent links between risk factors for schizophrenia (2016-2020)
Abstract
Evidence shows that; (a) neonatal vitamin D status is linked to risk of schizophrenia, and (b) genetic variants in genes related to voltage-gated calcium channels are associated with risk of schizophrenia. We have recently discovered that the active form of vitamin D modulates the function of particular types of voltage-gated calcium channels a subset of neurons in the prefrontal cortex. In the field of psychiatric research, it is unusual for clues from epidemiology, genetics and molecular neuroscience to converge on shared mechanisms. This applications pursues these discoveries in a focused and strategic fashion. Aim 1 will explore the mechanisms of action that link vitamin D to voltage gated calcium channels, with a focus on pharmacological probes to interrupt selected second messenger systems and the assessment of different receptor subunits in cell cultures. Aim 2 will characterize the vitamin D-responsive neurones that we have identified in the prefrontal cortex of Day 10 mice (using electrophysiology, immunohistology) and also examine other brain regions (e.g. hippocampus, nucleus accumbens). Aim 3 will explore if Developmental Vitamin D (DVD) deficiency results in alterations in the properties of the vitamin D responsive neurons (e.g. distribution, electrophysiological properties, immunohistological properties). By leveraging convergent clues from schizophrenia research we hope to efficiently reduce the scientific 'search space' and understand the pathogenesis of psychotic disorder
