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Vitamin D (VD3) Intensifies the Effects of Exercise and Prevents Alterations of Behavior, Brain Oxidative Stress, and Neuroinflammation, in Hemiparkinsonian Rats

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Abstract

In the present study, we investigated the effects of physical exercise in the presence of Vitamin D3 (VD3), on 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. The animals were divided into sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned plus VD3 (1 µg/kg, 21 days), in the absence (no exercise, NE) and presence (with exercise, WE) of physical exercise on a treadmill (30 min, speed of 20 cm/s, once a day/21 days). This procedure started, 24 h after the stereotaxic surgery (injections of 6-OHDA into the right striatum). The animals were then subjected to behavioral (rotarod, open field, and apomorphine tests) and their brain areas were dissected for neurochemical, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) determinations, and immunohistochemical studies for tyrosine hydroxylase (TH), dopamine transporter (DAT), and vitamin D receptor (VD3R). The effects on the brain oxidative stress: nitrite/nitrate, glutathione (GSH), and malondialdehyde (MDA) measurements were also evaluated. Behavioral changes of the 6-OHDA lesioned group were improved by exercise plus VD3. Similar results were observed in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations increased by exercise and VD3, compared with SO groups. Additionally, tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoexpressions were decreased in the 6-OHDA-lesioned groups, with values normalized after exercise and VD3. The VD3 receptor immunoexpression decreased in the 6-OHDA (NE) group, and this was attenuated by exercise, especially after VD3. While 6-OHDA lesions increased, VD3 supplementation decreased the oxidative stress, which was intensified by exercise. VD3 showed neuroprotective properties that were intensified by physical exercise. These VD3 actions on hemiparkinsonian rats are possibly related to its antioxidant and anti-inflammatory effects.

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Data Availability

All data generated or analyzed during this study are included in this manuscript. Further inquiries can be directed and are available upon request to the corresponding author.

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Acknowledgements

The authors are grateful to Prof. Francisco Vagnaldo Fechine Jamacuru and Prof. Héber José de Moura for their expertise in statistical data analyses, and also to Prof. M.O.L. Viana for the grammatical orthographic revision of the manuscript.

Funding

The authors are grateful for the financial support of the Brazilian National Research Council (CNPq), the Coordination for Improvement of Higher Level Personnel (CAPES), and the Foundation for Scientific and Technological Development Support of the State of Ceará (FUNCAP).

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Authors and Affiliations

  1. Graduate Program of Morphofunctional Sciences, Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil

    Roberta Oliveira da Costa, Ludmila Araújo Rodrigues Lima, Jalles Dantas de Lucena & Glauce Socorro de Barros Viana

  2. Graduate Program of Pharmacology, Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil

    Carlos Vinicius Jataí Gadelha-Filho, Pedro Everson Alexandre de Aquino, Wesley Lyeverton Correia Ribeiro, Francisco Arnaldo Viana Lima, Kelly Rose Tavares Neves & Glauce Socorro de Barros Viana

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  1. Roberta Oliveira da Costa
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Contributions

ROdC: Conducted all behavioral tests; CVJGF: Helped in handling and caring for the animals’ maintenance; PEAdA and LARL and JDdL: Carried out all the biochemical assays; WLCR: Responsible for the animal’s care and handling; FAVL and KRTN: Carried out all the immunohistochemical assays; GSdBV: Coordinated the project and wrote the final version of the manuscript, read and approved by all authors.

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Correspondence to Glauce Socorro de Barros Viana.

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The authors declare that they have no conflict of interest.

Ethical Approval

The research followed the ethical principles of the Brazilian National Council for Animal Experimentation (CONCEA). The study was submitted to and approved by the Animal Research Ethics Committee (CEPA) of the Faculty of Medicine of the Federal University of Ceará, under protocol number 82/2016. The experiments were performed according to the Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Academy of Sciences, Institute for Laboratory Animal Research (ILAR), in 2011. NIH (Office of Laboratory Animal Welfare).

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da Costa, R.O., Gadelha-Filho, C.V.J., de Aquino, P.E.A. et al. Vitamin D (VD3) Intensifies the Effects of Exercise and Prevents Alterations of Behavior, Brain Oxidative Stress, and Neuroinflammation, in Hemiparkinsonian Rats. Neurochem Res 48, 142–160 (2023). https://doi.org/10.1007/s11064-022-03728-4

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