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Vitamin D3 improves spatial memory and modulates cytokine levels in aged rats

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Abstract

Vitamin D3 deficiency is associated with an increased risk of dementia. An association between vitamin D3 deficiency and subjective cognitive complaints in geriatric patients has been previously reported. This study aimed to evaluate the effects of two doses of vitamin D3 on spatial memory (using the Radial Maze) and cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10)] on 2-, 6-, 13-, 22-, and 31-month-old male Wistar rats. Animals were supplemented with vitamin D3 at doses of 42 IU/kg and 420 IU/kg for 21 days. A radial maze test was performed to evaluate spatial memory. After the behavioral test, the frontal cortex and hippocampus were dissected for enzyme immunoassay analyses to measure the cytokine levels (TNFα, IL-1β, IL-6, and IL-10). Our results showed that vitamin D3 supplementation reversed spatial memory impairment at the supplemented doses (42 and 420 IU/kg) in 6-, 13-, and 22-month-old animals and at a dose of 420 IU/kg in 31-month-old animals. The lower dose (42 IU/kg) regulates both pro- and anti-inflammatory cytokines mainly in the frontal cortex. Our results suggest that vitamin D3 has a modulatory action on pro- and anti-inflammatory cytokines, since older animals showed increased cytokine levels compared to 2-month-old animals, and that vitamin D3 may exert an immunomodulatory effect on aging.

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Acknowledgements

We thank all funding agencies and authors for their contributions to this research.

Funding

The Laboratory of Experimental Neurology at the University of Southern Santa Catarina (UNESC) supported this study. Laboratory of Experimental Neurology (Brazil) is funded by grants from the National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), Foundation for the Support of Research and Innovation of the State of Santa Catarina (FAPESC) (JB – FAPESC N° 06/2017 – APOIO A GRUPOS DE PESQUISA DAS INSTITUIÇÕES DO SISTEMA ACAFE – TERMO DE OUTORGA N° 2018TR1551), UNESC and "For Women in Science" 2019, a program by L'oreal Brazil in partnership with UNESCO in Brazil and the Brazilian Academy of Sciences (ABC). JB, AGD, and TEAF were recipients of CNPq (Brazil) Productivity Fellowships.

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Authors and Affiliations

  1. Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina - UNESC, Criciúma, SC, 88806-000, Brazil

    Tatiani Bellettini-Santos, Michelle Lima Garcez, Francielle Mina, Natália Quadros Magnus, Nathalia de Souza Pereira, Ariandne de Oliveira Marques, Gabriela Serafim Keller, Gabriel Casagrande Zabot, Natália Baltazar do Nascimento, Eduarda Behenck Medeiros, Lisienny Campoli Tono Rempel & Josiane Budni

  2. Laboratory of Advanced Polymer Processing, Universidade Do Extremo Sul Catarinense - UNESC, Criciúma, SC, Brazil

    Tiago Elias Allievi Frizon & Alexandre Gonçalves Dal-Bó

  3. Department of Energy and Sustainability, Federal University of Santa Catarina – UFSC, Araranguá, SC, Brazil

    Tiago Elias Allievi Frizon

  4. Department of Health Education, Gerontology and Geriatrics, Jesuit University Ignatianum in Krakow, 31-501, Krakow, Poland

    Ewa Kucharska

  5. Graduate Program of Research and Extension (CEPEG), University Center of Espirito Santo, Colatina, ES, Brazil

    Tatiani Bellettini-Santos & Michelle Lima Garcez

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  1. Tatiani Bellettini-Santos
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Correspondence to Josiane Budni.

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Bellettini-Santos, T., Garcez, M.L., Mina, F. et al. Vitamin D3 improves spatial memory and modulates cytokine levels in aged rats. Metab Brain Dis 38, 1155–1166 (2023). https://doi.org/10.1007/s11011-022-01152-9

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