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Guanosine Promotes Proliferation in Neural Stem Cells from Hippocampus and Neurogenesis in Adult Mice

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Abstract

Neural stem cells can generate new neurons in the mouse adult brain in a complex multistep process called neurogenesis. Several factors regulate this process, including neurotransmitters, hormones, neurotrophic factors, pharmacological agents, and environmental factors. Purinergic signaling, mainly the adenosinergic system, takes part in neurogenesis, being involved in cell proliferation, migration, and differentiation. However, the role of the purine nucleoside guanosine in neurogenesis remains unclear. Here, we examined the effect of guanosine by using the neurosphere assay derived from neural stem cells of adult mice. We found that continuous treatment with guanosine increased the number of neurospheres, neural stem cell proliferation, and neuronal differentiation. The effect of guanosine to increase the number of neurospheres was reduced by removing adenosine from the culture medium. We next traced the neurogenic effect of guanosine in vivo. The intraperitoneal treatment of adult C57BL/6 mice with guanosine (8 mg/kg) for 26 days increased the number of dividing bromodeoxyuridine (BrdU)-positive cells and also increased neurogenesis, as identified by measuring doublecortin (DCX)-positive cells in the dentate gyrus (DG) of the hippocampus. Antidepressant-like behavior in adult mice accompanied the guanosine-induced neurogenesis in the DG. These results provide new evidence of a pro-neurogenic effect of guanosine on neural stem/progenitor cells, and it was associated in vivo with antidepressant-like effects.

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Funding

Research supported by grants from the Brazilian funding agencies to C.I.T.: CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)—INCT for Excitotoxicity and Neuroprotection; CNPq Productivity Fellowship. T.C.B.P. was the recipient of a post-doctoral fellowship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior- PAJT—88881.067963/2014-01), and B.S. was the recipient of a Master fellowship from CAPES. FGQBA received Ph.D. fellowship from CNPq.

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Authors and Affiliations

  1. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil

    Tetsade C. B. Piermartiri, Beatriz dos Santos & Carla Inês Tasca

  2. Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, UFSC, Florianópolis, SC, Brazil

    Tetsade C. B. Piermartiri, Beatriz dos Santos, Rui D. Prediger & Carla Inês Tasca

  3. Departamento de Farmacologia, Centro de Ciências Biológicas, UFSC, Florianópolis, SC, Brazil

    Fernanda G. Q. Barros-Aragão & Rui D. Prediger

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  1. Tetsade C. B. Piermartiri
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  2. Beatriz dos Santos
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  3. Fernanda G. Q. Barros-Aragão
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  4. Rui D. Prediger
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  5. Carla Inês Tasca
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Correspondence to Carla Inês Tasca.

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Experiments followed the “Principles of Laboratory Animal Care” (NIH 2011) and were approved by the Committee on the Ethics of Animal Experiments of the Federal University of Santa Catarina (CEUA/UFSC 1454270417).

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The authors declare that they have no conflict of interest.

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The financial support agencies had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Piermartiri, T.C.B., dos Santos, B., Barros-Aragão, F.G.Q. et al. Guanosine Promotes Proliferation in Neural Stem Cells from Hippocampus and Neurogenesis in Adult Mice. Mol Neurobiol 57, 3814–3826 (2020). https://doi.org/10.1007/s12035-020-01977-4

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  • DOI: https://doi.org/10.1007/s12035-020-01977-4

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