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Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.

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Acknowledgements

The authors acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul. We would like to thank Editage (www.editage.com) for English language editing.

Funding

This study was funded by Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS)—grant number: 19/2551–0001712-0). This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES—Finance code 001).

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Authors and Affiliations

  1. Laboratório de Neuroquímica, Inflamação E Câncer, Programa de Pós Graduação Em Bioquímica E Bioprospeção, Universidade Federal de Pelotas, Campus Capão do Leão, Pelotas, RS, 96010-900, Brazil

    Fernanda Cardoso Teixeira, Mayara Sandrielly Pereira Soares & Roselia Maria Spanevello

  2. Laboratório de Genômica Estrutural, Programa de Pós - Graduação Em Biotecnologia, Universidade Federal de Pelotas, Campus Capão do Leão, Pelotas, RS, Brazil

    Eduardo Bierhaus Blödorn, William Borges Domingues & Vinicius Farias Campos

  3. Laboratório de Enzimologia Toxicológica, Programa de Pós- Graduação Em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Karine Paula Reichert & Maria Rosa Chitolina

  4. Laboratório de Pesquisa Em Patologia, Programa de Pós - Graduação Em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Adriana Maria Zago, Fabiano Barbosa Carvalho, Jessie Martins Gutierres & Marilda da Cruz Fernandes

  5. Laboratório de Biologia Molecular, Universidade Federal de Goiás, Goiânia, GO, Brazil

    Relber Aguiar Gonçales

  6. Laboratório de Biomarcadores, Programa de Pós - Graduação Em Bioquímica E Bioprospecção, Universidade Federal de Pelotas, Campus Capão do Leão, Pelotas, RS, Brazil

    Francieli Moro Stefanello

Authors
  1. Fernanda Cardoso Teixeira
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  2. Mayara Sandrielly Pereira Soares
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  3. Eduardo Bierhaus Blödorn
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  4. William Borges Domingues
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  5. Karine Paula Reichert
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  6. Adriana Maria Zago
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  7. Fabiano Barbosa Carvalho
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  8. Jessie Martins Gutierres
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  9. Relber Aguiar Gonçales
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  10. Marilda da Cruz Fernandes
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  11. Vinicius Farias Campos
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  12. Maria Rosa Chitolina
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  13. Francieli Moro Stefanello
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  14. Roselia Maria Spanevello
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Contributions

Fernanda C. Teixeira, Jessié M. Gutierres, Mayara S.P. Soares: experimental design, animal treatment, memory behavior, biochemical analysis, statistical analysis, result interpretation, and manuscript preparation.

Eduardo B. Blödorn, William B. Domingues, Vinicius C. Farias: quantitative real-time polymerase chain reaction of BDNF and tyrosine receptor kinase B (TrkB).

Karine P. Reichert, Maria Rosa Chitolina: analysis of adenosine receptors.

Relber A. Gonçalves: cytokine analysis.

Adriana M. Zago, Fabiano B. Carvalho, Marilda C. Fernandes: histological analysis and immunoreactivity of glial fibrillary acid protein (GFAP) and synaptophysin.

Francieli M. Stefanello: experimental design and result interpretation.

Roselia M. Spanevello: experimental design, result interpretation, discussion, manuscript preparation, and funding.

Corresponding authors

Correspondence to Fernanda Cardoso Teixeira or Roselia Maria Spanevello.

Ethics declarations

Ethics Approval

The Committee of Ethics and Animal Experimentation of the Federal University of Pelotas, Brazil, under protocol number CEEA 4808–2017, approved all animal procedures. The use of animals was in accordance with the Brazilian Guidelines for the Care and Use of Animals in Scientific Research Activities (DBCA), which is in agreement with the National Council of Control of Animal Experimentation (CONCEA).

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Conflicts of Interest

The authors declare no competing interests.

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Teixeira, F.C., Soares, M.S.P., Blödorn, E.B. et al. Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer’s Disease. Mol Neurobiol 59, 841–855 (2022). https://doi.org/10.1007/s12035-021-02627-z

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  • DOI: https://doi.org/10.1007/s12035-021-02627-z

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