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Effects of chronic guanosine treatment on hippocampal damage and cognitive impairment of rats submitted to chronic cerebral hypoperfusion

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Abstract

Chronic cerebral hypoperfusion contributes to a cognitive decline related to brain disorders. Its experimental model in rats is a permanent bilateral common carotid artery occlusion (2VO). Overstimulation of the glutamatergic system excitotoxicity due to brain energetic disturbance in 2VO animals seems to play a pivotal role as a mechanism of cerebral damage. The nucleoside guanosine (GUO) exerts extracellular effects including antagonism of glutamatergic activity. Accordingly, our group demonstrated several neuroprotective effects of GUO against glutamatergic excitotoxicity. Therefore, in this study, we evaluated a chronic GUO treatment effects in rats submitted to 2VO. We evaluated the animals performance in the Morris water maze and hippocampal damage by neurons and astrocytes immunohistochemistry. In addition, we investigated the cerebrospinal fluid (CSF) brain derived neurotrophic factor (BDNF) and serum S100B levels. Additionally, the purine CSF and plasma levels were determined. GUO treatment did not prevent the cognitive impairment promoted by 2VO. However, none of the 2VO animals treated with GUO showed differences in the hippocampal regions compared to control, while 20% of 2VO rats not treated with GUO presented loss of pyramidal neurons and increased glial labeling cells in CA1 hippocampal region. In addition, we did not observe differences in CSF BDNF nor serum S100B levels among the groups. Of note, both the 2VO surgery and GUO treatment changed the purine CSF and plasma profile. In conclusion, GUO treatment did not prevent the cognitive impairment observed in 2VO animals, but our data suggest that GUO could be neuroprotective against hippocampal damage induced by 2VO.

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Acknowledgments

The authors are grateful to Rafael Berger Faraco, Vinicius Fornari Fernandes, Jocemar Ilha and Henrique Beck Biehl (laboratory technician) for their help in carrying out some of the experiments and Maria Elisa Calcagnotto for fruitful discussion. We also like to thank the Centro de Microscopia Eletrônica Confocal—UFRGS—(The Center of Confocal Microscopy—UFRGS) for the help with the microscopy technique used in this article. This research was supported by the Brazilian funding agencies FINEP “Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.08.42-00, CNPq, CAPES, FAPERGS, UFRGS and INCT for Excitotoxicity and Neuroprotection/CNPQ.

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  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos, 2600, anexo, Santana, Porto Alegre, RS, 90035-003, Brazil

    Marcelo Ganzella, Enderson Dias Alves de Oliveira, Daniel Diniz Comassetto, Victor Hermes Cereser Jr., Júlia Dubois Moreira, Gisele Hansel, Roberto Farina Almeida, Denise Barbosa Ramos, Debora Guerini Souza, Jean Pierre Oses, Paulo Valdeci Worm, Carlos Alexandre Netto & Diogo Onofre Souza

  2. Programa de Pós-graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Fernanda Cechetti, Matilde Achaval & Carlos Alexandre Netto

  3. Laboratorio de Farmacología Molecular, Centro de Investigación y Desarrollo de Medicamentos, Ciudad Habana, Cuba

    Yanier Nuñes Figueredo

  4. Laboratório de Neurociências Clínicas, Programa de Pós-Graduação em Saúde & Comportamento, Centro de Ciências da Vida e da Saúde, Universidade Católica de Pelotas, Almirante Barroso, 2012, Pelotas, RS, 96010-280, Brazil

    Jean Pierre Oses

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  1. Marcelo Ganzella
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  2. Enderson Dias Alves de Oliveira
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  3. Daniel Diniz Comassetto
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  4. Fernanda Cechetti
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  5. Victor Hermes Cereser Jr.
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  6. Júlia Dubois Moreira
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  7. Gisele Hansel
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  9. Denise Barbosa Ramos
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  10. Yanier Nuñes Figueredo
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  11. Debora Guerini Souza
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  12. Jean Pierre Oses
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  13. Paulo Valdeci Worm
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  14. Matilde Achaval
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  15. Carlos Alexandre Netto
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  16. Diogo Onofre Souza
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Correspondence to Marcelo Ganzella.

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Ganzella, M., de Oliveira, E.D.A., Comassetto, D.D. et al. Effects of chronic guanosine treatment on hippocampal damage and cognitive impairment of rats submitted to chronic cerebral hypoperfusion. Neurol Sci 33, 985–997 (2012). https://doi.org/10.1007/s10072-011-0872-1

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  • DOI: https://doi.org/10.1007/s10072-011-0872-1

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