EC Neurology

Vitamin D is a critical hormone that plays a pivotal role in various physiological processes, including bone health, calcium homeostasis, and the immune system. While vitamin D deficiency is common, excessive or prolonged intake can result in adverse effects. This study aimed to investigate the potential effects of vitamin D supplementation on locomotor activity, corticosterone levels, and glucocorticoid receptor regulation in the hippocampus. To accomplish this, male rats were randomly assigned to receive a low dose (2.5 mg/kg) and high dose (5 mg/kg) of vitamin D3 for 21 days. On day 20, open field activity was performed to assess locomotor activity. On day 21, rats were decapitated, and serum corticosterone levels were measured. Additionally, expression levels of glucocorticoid receptors in the hippocampus were analyzed using real-time PCR. Our findings suggest that vitamin D3 administration may increase stress in animals, as indicated by a reduction in exploratory activity in the open field test, an increase in serum corticosterone levels, and an upregulation of glucocorticoid receptors in the hippocampus. These results imply that vitamin D has a critical role in the regulation of the stress response and glucocorticoid signaling in the hippocampus. Moreover, caution should be exercised when determining the optimal dosage of vitamin D supplementation, as our results indicate that high doses may lead to adverse effects. In summary, our study provides new insights into the potential effects of vitamin D on the stress response and highlights the importance of carefully selecting the appropriate dose of vitamin D to avoid potential negative consequences.

Keywords Vitamin D; Open Field; Stress; Corticosterone; Glucocorticoid Receptor; Hippocampus

1. Heaney Robert P. "Guidelines for optimizing design and analysis of clinical studies of nutrient effects”. Nutrition Reviews1 (2014): 48-54.
2. Eyles Darryl W., et al. “Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function”. Psych Neuroendocrinology8 (2006): 958-964.
3. Eyles Darryl W., et al. “Distribution of the vitamin D receptor and 1α-hydroxylase in human brain”. Journal of Chemical Neuroanatomy1 (2005): 21-30.
4. Harris AP., et al. “Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and behaviour”. Psych Neuroendocrinology5 (2013): 648-658.
5. Gong Shuai., et al. “Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice”. PloS One2 (2015): e0117503.
6. Maletic Vladimir., et al. “Neurobiology of depression: an integrated view of key findings”. International Journal of Clinical Practice12 (2007): 2030-2040.
7. De Kloet., et al. “Stress and the brain: from adaptation to disease”. Nature Reviews Neuroscience6 (2005): 463-475.
8. De Kloet E Ronald., et al. “Brain corticosteroid receptor balance in health and disease”. Endocrine Reviews3 (1998): 269-301.
9. Joëls Marian. "Corticosteroid effects in the brain: U-shape it”. Trends in Pharmacological Sciences5 (2006): 244-250.
10. Revest Jean-Michel., et al. “The MAPK pathway and Egr-1 mediate stress-related behavioral effects of glucocorticoids”. Nature Neuroscience5 (2005): 664-672.
11. La Fleur Susanne E. "The effects of glucocorticoids on feeding behavior in rats”. Physiology and Behavior1 (2006): 110-114.
12. Pereira Alberto M., et al. “Neuropsychiatric disorders in Cushing’s syndrome”. Neuroendocrinology1 (2010): 65-70.
13. Fedotova Julia O. "Vitamin D 3 treatment differentially affects anxiety-like behavior in the old ovariectomized female rats and old ovariectomized female rats treated with low dose of 17β-estradiol”. BMC Medical Genetics 20 (2019): 45-56.
14. Ke Chun-Yen., et al. “Vitamin D3 reduces tissue damage and oxidative stress caused by exhaustive exercise”. International Journal of Medical Sciences2 (2016): 147.
15. Overeem Kathie., et al. “The impact of vitamin D deficiency on behaviour and brain function in rodents”. Current Opinion in Behavioral Sciences 7 (2016): 47-52.
16. Kesby James P., et al. “Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia”. Biological Psychiatry6 (2006): 591-596.
17. Eddn Asmaeil Zahour Gamal. “The effects of high doses vitamin d on anxiety and exploratory activity behaviours in rats. MS thesis”. Başkent Üniversitesi Sağlık Bilimleri Enstitüsü (2021).
18. Lightman SL., et al. “Hypothalamic-pituitary-adrenal function”. Archives of Physiology and Biochemistry1-2 (2002): 90-93.
19. Wang Qian., et al. “Glucocorticoid receptor protein expression in human hippocampus; stability with age”. Neurobiology of Aging6 (2013): 1662-1673.