Acute and chronic sleep deprivation effects in the regulatory pathway of vitamin D in an animal model

• Grant number: 16/02205-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Monica Levy Andersen
• Grantee: Daniela Leite de Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Vitamin D plays an important role in the osteomineral metabolism. Its synthesis is regulated by CYP2R1, CYP24A1 and CYP27B1 enzymes as well as the vitamin D receptor (VDR), which binds to the active form of vitamin D modulating gene expression. Studies have demonstrated an association between vitamin D deficit and several pathological conditions such as infections and autoimmune diseases, and more recently sleep disorders such as obstructive sleep apnea and sleepiness. It is known that CYP27B1 and VDR molecules are present in different regions of the central nervous system, including the hypothalamus, which is actively involved in regulating the sleep-wake cycle. However, clinical studies have shown methodological limitations that difficult the understanding of the relationship between sleep and vitamin D. Thus, the use of animal models of sleep deprivation may allow the advancement of this research line, since vitamin D levels in rodents have similarity to humans. The objective of this study is to evaluate the effects of acute and chronic sleep deprivation in the regulatory pathway of vitamin D in an animal model. For this, 70 adult male Wistar rats will be distributed into 7 groups: paradoxical sleep deprivation during 24, 48, 72 and 96 h, total sleep deprivation for 6 h and sleep restriction for 21 days. At the end of the protocol, the animals will be euthanized and blood will be collected for biochemical evaluation of serum levels of 25(OH)D, 1-±25(OH)2D, Ca2+, parathyroid hormone and corticosterone. Tissue fragments of brain, liver and kidney will be collected to evaluate the protein and gene expression by Western blot and qPCR. We expect to observe biochemical, protein and gene changes in the regulatory pathway of vitamin D due to sleep disturbance conditions and thus to further understand the mechanisms involved in the relationship between sleep and vitamin D.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE OLIVEIRA, DANIELA LEITE; HIROTSU, CAMILA; TUFIK, SERGIO; ANDERSEN, MONICA LEVY. The interfaces between vitamin D, sleep and pain. Journal of Endocrinology, v. 234, n. 1, p. R23-R36, JUL 2017. (14/15259-2, 16/02205-7)

DE OLIVEIRA, DANIELA LEITE; DOKKEDAL-SILVA, VINICIUS; FERNANDES, GUILHERME LUIZ; KIM, LENISE JIHE; TUFIK, SERGIO; ANDERSEN, MONICA LEVY. Sleep duration as an independent factor associated with vitamin D levels in the EPISONO cohort. JOURNAL OF CLINICAL SLEEP MEDICINE, v. 17, n. 12, p. 2439-2449, DEC 1 2021. (16/02205-7, 15/19136-5)