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Effects of cholecalciferol on behavior and production of reactive oxygen species in female mice subjected to corticosterone-induced model of depression

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Abstract

Major depressive disorder (or depression) is one of the most frequent psychiatric illnesses in the population, with chronic stress being one of the main etiological factors. Studies have shown that cholecalciferol supplementation can lead to attenuation of the depressive state; however, the biochemical mechanisms involved in the relationship between cholecalciferol and depression are not very well known. The objective of this study was to investigate the effects of the administration of cholecalciferol on behavioral parameters (tail suspension test (TST), open field test (OFT), splash test (ST)) and redox state (dichlorofluorescein (DCF)) in adult female Swiss mice subjected to a model of depression induced by chronic corticosterone treatment. Corticosterone (20 mg/kg, p.o.) was administered once a day for 21 days. For investigation of the antidepressant-like effect, cholecalciferol (100 IU/kg) or fluoxetine (10 mg/kg, positive control) was administered p.o. within the last 7 days of corticosterone administration. After the treatments, the behavioral tests and biochemical analyses in the hippocampus and prefrontal cortex of the rodent samples were performed. Animals submitted to repeated corticosterone administration showed a depressive-like behavior, evidenced by a significant increase in the immobility time in the TST, which was significantly reduced by the administration of cholecalciferol or fluoxetine. In addition, the groups treated with cholecalciferol and fluoxetine showed a significant decrease in the production of reactive oxygen species (ROS) in the hippocampus. These results show that cholecalciferol, similar to fluoxetine, has a potential antidepressant-like effect, which may be related to the lower ROS production.

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Abbreviations

DCF:

Dichlorofluorescein

DCFH:

2,7 Dichlorofluorescein

DMSO:

Dimethylsulfoxide

ROS:

Reactive oxygen species

HPA:

Hypothalamic-pituitary-adrenal

NADPH:

Nicotinamide adenine dinucleotide phosphate

OFT:

Open field test

ST:

Splash test

TNF:

Forced swim test

TST:

Tail suspension test

VDR:

Vitamin D receptor

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Author contribution statement

MM and ALSR conceived and designed research. SVSS, PBR, VBN, and MM conducted experiments. SVSS, PBR, JDM, and MM analyzed data. SVSS, JDM, and MM wrote the manuscript. All authors read and approved the manuscript.

Funding

This study was financially supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant numbers 150082/2018-5 and 310113/2017-2], and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). ALSR is CNPq Research Fellow.

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Authors and Affiliations

  1. Graduate Program in Nutrition, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Suene Vanessa da Silva Souza & Júlia Dubois Moreira

  2. Biochemistry Department, Biological Science Center, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Priscila Batista da Rosa, Vivian Binder Neis, Ana Lúcia S. Rodrigues & Morgana Moretti

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  1. Suene Vanessa da Silva Souza
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  2. Priscila Batista da Rosa
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  3. Vivian Binder Neis
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  5. Ana Lúcia S. Rodrigues
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Correspondence to Morgana Moretti.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Ethics Committee CEUA PP00795).

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da Silva Souza, S.V., da Rosa, P.B., Neis, V.B. et al. Effects of cholecalciferol on behavior and production of reactive oxygen species in female mice subjected to corticosterone-induced model of depression. Naunyn-Schmiedeberg's Arch Pharmacol 393, 111–120 (2020). https://doi.org/10.1007/s00210-019-01714-2

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