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Protective Effects of Kefir Against Unpredictable Chronic Stress Alterations in Mice Central Nervous System, Heart, and Kidney

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Abstract

Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney.

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Acknowledgements

The authors acknowledge the support of Alexandre Giusti Paiva and Giovane Galdino.

Funding

The research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq, 406177/2016–3), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG, PPM-00383–18), and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Alessandra Oliveira Silva, Larissa Helena Torres, and Carla Speroni Ceron conceived and designed the research. Alessandra Oliveira Silva, Jéssyca Milene Ribeiro, Talita Barbará Patrocínio, Gabriel Estevam Amorim, Antônio Alves Pereira-Júnior, and Marilene Lopes Ângelo conducted experiments. Fernanda Borges de Araújo Paula, Marcos Vinícios Salles Dias, Nelma de Mello Silva Oliveira, Larissa Helena Torres, José Antunes-Rodrigues, and Lucila Leico Kagohara Elias contributed with reagents or analytical tools. Alessandra Oliveira Silva, Sílvia Graciela Ruginsk and Carla Speroni Ceron analyzed data. Alessandra Oliveira Silva and Carla Speroni Ceron wrote the manuscript. All authors reviewed and approved the manuscript. All authors of the paper have fulfilled the criteria for authorship.

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Silva, A.O., Ribeiro, J.M., Patrocínio, T.B. et al. Protective Effects of Kefir Against Unpredictable Chronic Stress Alterations in Mice Central Nervous System, Heart, and Kidney. Probiotics & Antimicro. Prot. 15, 411–423 (2023). https://doi.org/10.1007/s12602-022-10031-9

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