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Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

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Abstract

Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

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Data Availability

The datasets generated and/or analyzed during the current study are available in the Open Science Framework repository, https://doi.org/10.17605/OSF.IO/K7CX3.

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Acknowledgements

This work was supported by the Brazilian Agencies/Programs FAPERGS #1010267, FAPERGS/PPSUS#17/2551-0001, FAPERGS/PRONEX#16/2551-0000499-4, Programa de Internacionalização de Ciência FAPERGS/CAPES #19/25510000717-5, Program Science without Borders CNPQ #4011645/2012-6, and CNPq INNT #5465346/2014-6.

Funding

Fundiing was provided by FAPERGS (#1010267), FAPERGS/PPSUS (#17/2551-0001), FAPERGS/PRONEX (#16/2551-0000499-4), FAPERGS/CAPES (#19/25510000717-5) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (#4011645/2012-6, #5465346/2014-6).

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Authors and Affiliations

  1. Laboratory of Neurotrauma and Biomarkers, Departamento de Bioquímica, ICBS, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

    N. R. Strogulski, A. Kopczynski, V. G. de Oliveira, R. B. Carteri, M. S. Rodolphi & L. V. Portela

  2. Neuroinflammation and Neuroimmunology Laboratory, Brain Institute of Rio Grande Do Sul, Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil

    G. Hansel

  3. Brain Institute of Rio Grande Do Sul (BraIns), Pontifical Catholic University of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil

    G. T. Venturin, S. Greggio & J. C. DaCosta

  4. Zimmer Neuroimaging Lab, Departamento de Bioquímica, ICBS, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

    M. A. De Bastiani

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  1. N. R. Strogulski
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Contributions

All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by NRS, AK, VGDeO, RBC, and MSR. Micro-PET FDG preparation, processing, and analysis were performed by GV, and SG. MAdeB performed the brain connectivity analysis. JCdaC and LVP acquired funding. The first draft of the manuscript was written by NRS, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to L. V. Portela.

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Strogulski, N.R., Kopczynski, A., de Oliveira, V.G. et al. Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice. Neurochem Res 47, 2032–2042 (2022). https://doi.org/10.1007/s11064-022-03592-2

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