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Effects of long-term resveratrol treatment in hypothalamic astrocyte cultures from aged rats

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Abstract

Aging is intrinsically related to metabolic changes and characterized by the accumulation of oxidative and inflammatory damage, as well as alterations in gene expression and activity of several signaling pathways, which in turn impact on homeostatic responses of the body. Hypothalamus is a brain region most related to these responses, and increasing evidence has highlighted a critical role of astrocytes in hypothalamic homeostatic functions, particularly during aging process. The purpose of this study was to investigate the in vitro effects of a chronic treatment with resveratrol (1 µM during 15 days, which was replaced once every 3 days), a recognized anti-inflammatory and antioxidant molecule, in primary hypothalamic astrocyte cultures obtained from aged rats (24 months old). We observed that aging process changes metabolic, oxidative, inflammatory, and senescence parameters, as well as glial markers, while long-term resveratrol treatment prevented these effects. In addition, resveratrol upregulated key signaling pathways associated with cellular homeostasis, including adenosine receptors, nuclear factor erythroid-derived 2-like 2 (Nrf2), heme oxygenase 1 (HO-1), sirtuin 1 (SIRT1), proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and phosphoinositide 3-kinase (PI3K). Our data corroborate the glioprotective effect of resveratrol in aged hypothalamic astrocytes, reinforcing the beneficial role of resveratrol in the aging process.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors of this study are supported by Universidade Federal do Rio Grande do Sul (UFRGS), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

Funding

This work was supported by Universidade Federal do Rio Grande do Sul (UFRGS), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

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VS, LDB, CLS, and MB performed the experiments. CAG, GL, and AQS provided resources and materials/chemicals. All authors contributed to the experimental design, interpretation of the results, and writing of the paper. All authors revised and approved the manuscript.

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Correspondence to André Quincozes-Santos.

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All animal experiments were performed by following per under the National Institute of Health (NIH) Guide for the Care and Use of Laboratory Animals and Brazil’s National Council for the Control of Animal Experimentation (CONCEA). The experimental protocols were approved by the Federal University of Rio Grande do Sul Animal Care and Use Committee (process number 35387).

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Sovrani, V., Bobermin, L.D., Santos, C.L. et al. Effects of long-term resveratrol treatment in hypothalamic astrocyte cultures from aged rats. Mol Cell Biochem 478, 1205–1216 (2023). https://doi.org/10.1007/s11010-022-04585-z

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