​Gevork Salmastyan, Class of 2019

Vitamin D is an important player in the functioning of our nervous systems. This fat-soluble vitamin we get from sunlight and food has neuroprotective properties and is also involved in the development and survival of neurons. Previous studies have shown that deficiency in vitamin D is associated with cognitive and psychiatric disorders such as schizophrenia (Cieslak et al. 2014), depression (Brouwer-Brolsma et al. 2016), dementia (Afzal et al. 2014), multiple sclerosis (Goral et al. 2015) and autism (Fernell et al. 2015). Other studies conducted on elderly people have yielded inconsistent results for the association between vitamin D deficiency and cognitive impairment (Annweiler et al. 2013, Littlejohns et al. 2016). Animal studies have also that vitamin D deficiency has an effect on memory and learning, but results have also been inconsistent (Byrne et al. 2013, Taghizadeh et al. 2013).

A new paper published in Brain Structure and Function aims to make this relationship between vitamin D and brain function clearer. Researchers Al-Amin, Sullivan, Kurniawan, and Burne at the Queensland Brain Institute had the goal of examining the effect adult vitamin D deficiency has on hippocampal-dependent spatial learning hippocampus volume/size and neural connectivity in adult mice. The researchers fed one group of 10-week-old mice vitamin D-rich diet, and fed another group a vitamin D-deficient diet. The authors hypothesized that vitamin D deficiency would be associated with spatial learning problems and a decrease in volume of hippocampal sub-regions. Brain structure was examined by MRI, and immunohistochemistry was performed to examine perineuronal nets and parvalbumin interneurons in the brains. Perineuronal nets are extracellular matrix structures that stabilize synapses in the adult brain, thus having a role in plasticity and memory formation; parvalbumin is a globular protein involved in calcium signaling involved in many physiological processes.  They subjected the mice to a behavioral spatial learning task called active place avoidance that involves treating the mice with an electric shock if they enter a designated shock zone in a testing space. They also tested the muscle and motor coordination of the mice by examining their rotarod and grip strength to ensure that the results from the spatial learning task were affected only by hippocampal function, not due to impaired motor function or poor muscle strength.

The adult vitamin D deficient mice had a lower latency to enter the shock area in the active place avoidance task compared to the vitamin D diet mice. The researchers suggested this lower latency meant that there was damaged hippocampal-dependent spatial learning in the vitamin D deficient mice. The rotarod and grip strength tests revealed no differences between the control and test mice, which suggests that vitamin D deficiency had no significant effect on motor coordination or muscle strength and that the active place avoidance task was dependent on hippocampus function. Analysis on brain structures revealed that there were connection deficits in 29 brain regions of the vitamin D deficient mice. But, structural image analysis showed that the deficiency had no effect on the global hippocampal volume. Yet the area with the greatest disrupted connections was the right hippocampus in vitamin D deficient mice. Furthermore, perineuronal net expression was significantly reduced in regions of the hippocampus for deficient mice, and there was no significant effect of type of diet on parvalbumin expression in the hippocampus. This reduction in perineuronal net expression in the hippocampus is associated with the spatial learning deficit in the vitamin deficient mice.

Ultimately, the results of the study are another entry in the literature examining the relationship between the important steroid vitamin D and the enigmatic functioning of the brain. The authors believe the results are evidence demonstrating adult vitamin D deficiency in healthy mice has an instrumental role in hippocampal dependent learning and the formation of memories. The authors suggest that these disruptions in learning could be explained by the disorganized connections in the right hippocampus.
 
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References
1. Al-Amin, M.M., Sullivan, R.K.P., Kurniawan, N.D. et al. Brain Struct Funct (2019). https://doi.org/10.1007/s00429-019-01840-w
 
2. Annweiler C, Montero-Odasso M, Hachinski V, Seshadri S, Bartha R, Beauchet O (2013) Vitamin D concentration and lateral cerebral ventricle volume in older adults. Mol Nutr food Res 57(2):267–276. https ://doi.org/10.1002/mnfr.20120 0418
 
3. Afzal S, Bojesen SE, Nordestgaard BG (2014) Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 10(3):296–302.
https://doi.org/10.1016/j.jalz.2013.05.1765
 
4. Brouwer-Brolsma EM, Dhonukshe-Rutten RA, van Wijngaarden JP, van der Zwaluw NL, Sohl E, In’t Veld PH, van Dijk SC, Swart KM, Enneman AW, Ham AC, van Schoor NM, van der Velde N,Uitterlinden AG, Lips P, Feskens EJ, de Groot LC (2016) Low vitamin D status is associated with more depressive symptoms in Dutch older adults. Eur J Nutr 55(4):1525–1534. https ://doi.org/10.1007/s0039 4-015-0970-6
 
5. Byrne JH, Voogt M, Turner KM, Eyles DW, McGrath JJ, Burne TH (2013) The impact of adult vitamin D deficiency on behavior and brain function in male Sprague-Dawley rats. PloS one
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6. Cieslak K, Feingold J, Antonius D, Walsh-Messinger J, Dracxler R, Rosedale M, Aujero N, Keefe D, Goetz D, Goetz R, Malaspina D (2014) Low vitamin D levels predict clinical features of schizophrenia. Schizophr Res 159(2–3):543–545. https://doi.org/10.1016/j.schres.2014.08.031
 
7. Fernell E, Bejerot S, Westerlund J, Miniscalco C, Simila H, Eyles D, Gillberg C, Humble MB (2015) Autism spectrum disorder and low vitamin D at birth: a sibling control study. Mol Autism 6:3. https ://doi.org/10.1186/2040-2392-6-3
 
8. Goral A, Brola W, Kasprzyk M, Przybylski W (2015) The role of vitamin D in the pathogenesis and course of multiple sclerosis. Wiad Lek 68(1):60–66
 
9. Littlejohns TJ, Kos K, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Llewellyn DJ (2016) Vitamin D and risk of neuroimaging abnormalities. PloS One 11(5):e0154896.
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