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Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions

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Abstract

Rationale

Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions.

Objective

The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer’s disease (AD) induced by streptozotocin (STZ).

Methods

Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50 mg/kg), and STZ plus inosine (100 mg/kg). STZ (3 mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25 days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus.

Results

The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain.

Conclusions

Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.

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Acknowledgments

This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS). This study was financed in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)—Finance code 001. R.M.S. is recipient of CNPq fellowship (309299/2017-9).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil

    Fernanda Cardoso Teixeira, Mayara Sandrielly Pereira Soares, Bruna da Siveira de Mattos, Luiza Spohr, Carlus Augustu Tavares do Couto, Natália Pontes Bona, Francieli Moro Stefanello & Roselia Maria Spanevello

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

    Jessié Martins Gutierres

  3. Programa de Pós-Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Charles Elias Assmann & Vera Maria Morsch

  4. Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Ivana Beatrice Mânica da Cruz

  5. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário, Capão do Leão, Pelotas, RS, 96010-900, Brazil

    Roselia Maria Spanevello

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  1. Fernanda Cardoso Teixeira
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Correspondence to Roselia Maria Spanevello.

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Teixeira, F.C., Gutierres, J.M., Soares, M.S.P. et al. Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions. Psychopharmacology 237, 811–823 (2020). https://doi.org/10.1007/s00213-019-05419-5

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