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Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities

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Abstract

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer’s disease.

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Acknowledgements

We thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul. This study was also financed in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES—Finance code 001). We would like to thank Editage (www.editage.com) for English language editing.

Funding

This research was supported by Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS Grant Number—19/2551-0001712-0).

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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, Bruna da Silveira de Mattos, Julia Eisenhardt de Mello, Juliane Cardoso, Luiza Spohr, Karina Pereira Luduvico, Mayara Sandrielly Pereira Soares, 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

    Fabiano Barbosa Carvalho & Jessie Martins Gutierres

  3. Biotério Central, Universidade Federal de Pelotas, Pelotas, RS, Brazil

    Anelize de Oliveira Campello Felix

  4. 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

    Fernanda Cardoso Teixeira & Roselia Maria Spanevello

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  1. Fernanda Cardoso Teixeira
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Contributions

Conceptualization (FCT, JMG, RMS), data curation (BSM, JEM, JC, LS, KPL), formal analysis (FCT, MSPS), funding acquisition (FMS, RMS), animals procedures (FCT, AOCF, BSM, JEM, JC), biochemical analysis (FCT, LS, KPL, MSPS), manuscript elaboration and review (FCT, FC, JMG, RMS).

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Correspondence to Fernanda Cardoso Teixeira or Roselia Maria Spanevello.

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All animal experimental protocols were approved by the Committee of Ethics and Animal Experimentation of the Federal University of Pelotas, RS, Brazil (Protocol Number: CEEA 4808- 2017).

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Teixeira, F.C., de Mattos, B.S., Mello, J.E. et al. Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities. Neurochem Res 47, 446–460 (2022). https://doi.org/10.1007/s11064-021-03460-5

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