Abstract
The search for strategies to develop resilience against metabolic and neuropsychiatric disorders has motivated the clinical and experimental assessment of early life interventions such as lifestyle-based and use of unconventional pharmacological compounds. In this study, we assessed the effects of voluntary physical activity and 7,8-Dihydroxy-4-methylcoumarin (DHMC), independently or in combination, over mice physiological and behavioral parameters, adult hippocampal and hypothalamic neurogenesis, and neurotrophic factors expression in the hypothalamus. C57Bl/6J mice were submitted to a 29-day treatment with DHMC and allowed free access to a running wheel. We found that DHMC treatment alone reduced fasting blood glucose levels. Moreover, physical activity showed an anxiolytic effect in the elevated plus maze task and DHMC produced additional anxiolytic behavior, evidenced by reduced activity during the light cycle in the physical activity group. Although we did not find any differences in hypothalamic or hippocampal adult neurogenesis, DHMC increased gene expression levels of VEGF, which was correlated to the reduced fasting glucose levels. In conclusion, our data emphasize the potential of physical activity in reducing development of neuropsychiatric conditions, such as anxiety, and highlights DHMC as an attractive compound to be investigated in future studies addressing neuropsychiatric disorders associated with metabolic conditions.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank the access to equipment and assistance provided by the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the State University of Campinas.
Funding
The study was supported by Grants from the Minas Gerais Research Support Foundation (FAPEMIG), Conselho Nacional de Pesquisa e Desenvolvimento Cientifico (CNPq), São Paulo Research Foundation (2013/07607-8), and financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES); INFABIC is co-funded by São Paulo Research Foundation (FAPESP) (2014/50938-8) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (465699/2014-6).
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PKFL and DFE performed experiments and analyzed the data; MSAM and NOB assisted voluntary physical activity experiments. SST guided the DMHC synthesis process. LAV provision of materials and aid for molecular analysis. PKFL and DFE wrote the manuscript; RFM designed the study; all authors revised and approved the final version of the manuscript.
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All experimental procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, with the approval of the Ethics Committee of the Federal University of Lavras/Brazil and Animal Experiments Control Council (CONCEA), according to protocol nº 078/17.
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Lopes, P.K.F., Engel, D.F., Bertolini, N.O. et al. Behavioral, neuroplasticity and metabolic effects of 7,8-dihydroxy-4-methylcoumarin associated with physical activity in mice. Metab Brain Dis 36, 2425–2436 (2021). https://doi.org/10.1007/s11011-021-00849-7
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DOI: https://doi.org/10.1007/s11011-021-00849-7