Hypothesis – Brain plasticity improved by Vitamin D – Feb 2019

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

Brain Structure and Function and Trends in Neuroscience., Cell https://doi.org/10.1016/j.tins.2019.01.003
Phoebe E. Mayne 1 and Thomas H.J. Burne ®1,2’ t.burne at uq.edu.au
1 Queensland Brain Institute, the University of Queensland, St Lucia, QLD 4072, Australia
2 Queensland Centre for Mental Health Research, Wacol, QLD

 Download the PDF from VitaminDWiki
Highlights

• 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.

Vitamin D deficiency affects nearly a billion people worldwide [1]. In addition to its established roles in causing rickets and osteomalacia, the convergence of in vitro animal and epidemiological research points to vitamin D deficiency as a candidate modifiable risk factor for a range of neuropsychiatric and neurological diseases [1]. While definitive links remain to be substantiated, vitamin D deficiency has been associated with vulnerability to various disorders including

• schizophrenia [2],
• depression [3],
• attention deficit disorder [4],
• autism spectrum disorder [5], and
• neurodegenerative disorders such as Alzheimer's disease and dementia [6].

A common thread to all of these disorders is impairment in cognitive functioning, which is also the most salient predictor of functional outcome. Therefore, it is essential to identify risk factors that operate at the early stages of disease, and to develop efficient primary treatment strategies to delay or prevent cognitive disturbances. This review aims to outline recent developments in our understanding of the physiological roles of vitamin D, and the impact of vitamin D deficiency on the presentation of cognitive deficits. Furthermore, we discuss evidence indicating that vitamin D deficiency may disturb properties of brain plasticity, which is likely to contribute to the presentation of cognitive disturbances. Lastly, we expound on a novel hypothesis, suggesting a link between vitamin D and PNNs, aggregate structures of the ECM

Figure 2. Schematic Outline Depicting How Vitamin D May Impactthe Integrity of PNNs in a Disease State. A neuron (brown) is depicted on the left, and a neuron with a PNN (green mesh) is depicted on the right. Collagen fibres (green) and the polysaccharides (purple) represent the loosely organised ECM, which exists ubiquitously throughout the brain and spinal cord. Vitamin D deficiency may impact the flow of calcium through L-VGCCs (depicted on the surface of the neuron) via genomic actions, moderating the transcription of L-VGCCs, and nongenomic actions, rapidly activating protein kinases such as CaMKII, PKA, and PI3K, which then facilitates calcium influx via L-VGCCs. These changes in calcium likely contribute to changes in nNOS, resulting in abnormal secretion of NO into the extracellular space. This abnormal NO secretion may increase MMP-9 levels, which are likely to impact both the ECM and aggrecan-rich PNNs, resulting in a decrease of PNN-positive cells. This decrease may perturb the excitation-inhibition balance in neuronal circuits, particularly through destabilising the activity of GABAergic interneurons that express parvalbumin. Ultimately this may produce network dysfunction resulting in the presentation of cognitive deficits.
Abbreviations:
CaMKII, calcium/ calmodulin-dependent protein kinase II;
ECM, extracellular matrix;
L-VGCC, L-type voltage-gated calcium channel;
MMP- 9, matrix metalloproteinase-9;
NO, nitric oxide;
nNOS, neural NO synthase;
PNN, perineuronal net;
Vit D, vitamin D.