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Anti-aging effects of guanosine in glial cells

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Abstract

Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality. Thus, the search for molecules able to reduce the glial dysfunction associated with aging may represent an approach for avoiding the onset of age-related neurological diseases. Hence, the aim of this study was to evaluate the anti-aging effects of guanosine, using primary astrocyte cultures from newborn, adult, and aged Wistar rats. Concomitantly, we evaluated the role of heme oxygenase 1 (HO-1) in guanosine-mediated glioprotection. We observed age-dependent changes in glutamate uptake, glutamine synthetase (GS) activity, the glutathione (GSH) system, pro-inflammatory cytokine (tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)) release, and the transcriptional activity of nuclear factor kB (NFkB), which were prevented by guanosine in an HO-1-dependent manner. Our findings suggest guanosine to be a promising therapeutic agent able to provide glioprotection during the aging process. Thus, this study contributes to the understanding of the cellular and molecular mechanisms of guanosine in the aging process.

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Acknowledgments

This work was supported by 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), Financiadora de Estudos e Projetos (FINEP)-Instituto Brasileiro de Neurociências (IBN Net) 01.06.0842-00, Universidade Federal do Rio Grande do Sul (UFRGS), and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

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  1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, RS, Brazil

    Débora Guerini Souza, Bruna Bellaver, Larissa Daniele Bobermin, Diogo Onofre Souza & André Quincozes-Santos

  2. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, RS, Brazil

    Diogo Onofre Souza & André Quincozes-Santos

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  1. Débora Guerini Souza
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Souza, D.G., Bellaver, B., Bobermin, L.D. et al. Anti-aging effects of guanosine in glial cells. Purinergic Signalling 12, 697–706 (2016). https://doi.org/10.1007/s11302-016-9533-4

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