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Molecular Neurobiology

, Volume 54, Issue 4, pp 2790–2800 | Cite as

Hypoxanthine Intrastriatal Administration Alters Neuroinflammatory Profile and Redox Status in Striatum of Infant and Young Adult Rats

  • Helena Biasibetti
  • Paula Pierozan
  • André Felipe Rodrigues
  • Vanusa Manfredini
  • Angela T. S. Wyse
Article

Abstract

Hypoxanthine, the major oxypurine metabolite involved in purine’s salvage pathway in the brain, is accumulated in Lesch-Nyhan disease, an inborn error of metabolism of purine. The purpose of this study was to investigate the effects of hypoxanthine intrastriatal administration on infant and young adult rats submitted to stereotactic surgery. We analyzed the effect of hypoxanthine on neuroinflammatory parameters, such as cytokine levels, immunocontent of NF-κB/p65 subunit, iNOS immunocontent, nitrite levels, as well as IBA1 and GFAP immunocontent in striatum of infant and young adult rats. We also evaluate some oxidative parameters, including reactive species production, superoxide dismutase, catalase, glutathione peroxidase activities, as well as DNA damage. Wistar rats of 21 and 60 days of life underwent stereotactic surgery and were divided into two groups: control (infusion of saline 0.9 %) and hypoxanthine (10 μM). Intrastriatal administration of hypoxanthine increased IL-6 levels in striatum of both ages of rats tested, while TNF-α increased only in 21-day-old rats. Hypoxanthine also increased nuclear immunocontent of NF-κB/p65 subunit in striatum of both ages of rats. Nitrite levels were decreased in striatum of 21-day-old rats; however, the immunocontent of iNOS was increased in striatum of hypoxanthine groups. Microglial and astrocyte activation was seen by the increase in IBA1 and GFAP immunocontent, respectively, in striatum of infant rats. All oxidative parameters were altered, suggesting a strong neurotoxic hypoxanthine role on oxidative stress. According to our results, hypoxanthine intrastriatal administration increases neuroinflammatory parameters perhaps through oxidative misbalance, suggesting that this process may be involved, at least in part, to neurological disorders found in patients with Lesch-Nyhan disease.

Keywords

Hypoxanthine Neuroinflammation Microglial and astrocyte markers DNA damage Lesch-Nyhan disease 

Notes

Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil).

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Helena Biasibetti
    • 1
  • Paula Pierozan
    • 1
  • André Felipe Rodrigues
    • 1
  • Vanusa Manfredini
    • 2
  • Angela T. S. Wyse
    • 1
    • 3
  1. 1.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBSUFRGSPorto AlegreBrazil
  2. 2.Universidade Federal do PampaUruguaianaBrazil
  3. 3.Laboratório de Neuroproteção e Doenças Neurometabólicas. Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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