Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness

Vitamin D plays various roles in normal brain physiology, including modulating synaptic plasticity. Converging evidence suggests that vitamin D deficiency affects multiple brain processes, including cognitive functioning, in both healthy people and those afflicted with neuropsychiatric illness. The underlying mechanisms, however, are poorly understood. Evidence suggests that vitamin D deficiency impacts synaptic plasticity through a plethora of avenues, including l-type voltage-gated calcium channels and regulation of various neurotransmitters, including NO. An emerging concept is that vitamin D deficiency may weaken the integrity of PNNs, aggregates of the ECM, through modulation of MMPs. PNNs have been reported to play essential roles in cognitive processes such as learning and memory. As such, dysregulation of PNNs is likely to disturb neural-circuit function and impair cognitive functioning. Assessing the molecular mechanisms that underpin the roles of vitamin D in cognition is pertinent to informing preventive and intervention strategies for persons with cognitive disturbances, including patients with schizophrenia. Over a billion people worldwide are affected by vitamin D deficiency. Although vitamin D deficiency is associated with impaired cognition, the mechanisms mediating this link are poorly understood. The extracellular matrix (ECM) has now emerged as an important participant of synaptic plasticity and a new hypothesis is that vitamin D may interact with aggregates of the ECM, perineuronal nets (PNNs), to regulate brain plasticity. Dysregulation of PNNs caused by vitamin D deficiency may contribute to the presentation of cognitive deficits. Understanding the molecular mechanisms underpinning the role of vitamin D in brain plasticity and cognition could help identify ways to treat cognitive symptoms in schizophrenia and other neuropsychiatric conditions. Over a billion people worldwide are affected by vitamin D deficiency. Although vitamin D deficiency is associated with impaired cognition, the mechanisms mediating this link are poorly understood. The extracellular matrix (ECM) has now emerged as an important participant of synaptic plasticity and a new hypothesis is that vitamin D may interact with aggregates of the ECM, perineuronal nets (PNNs), to regulate brain plasticity. Dysregulation of PNNs caused by vitamin D deficiency may contribute to the presentation of cognitive deficits. Understanding the molecular mechanisms underpinning the role of vitamin D in brain plasticity and cognition could help identify ways to treat cognitive symptoms in schizophrenia and other neuropsychiatric conditions.