Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure

Abstract

Systemic inflammation triggered by lipopolysaccharide (LPS) administration disrupts blood–brain barrier (BBB) homeostasis in animal models. This event leads to increased susceptibility of several encephalic structures to potential neurotoxicants present in the bloodstream. In this study, we investigated the effects of alternate intraperitoneal injections of LPS on BBB permeability, social recognition memory and biochemical parameters in the striatum 24 h and 60 days after treatments. In addition, we investigated whether the exposure to a moderate neurotoxic dose of the herbicide paraquat could potentiate LPS-induced neurotoxicity. LPS administration caused a transient disruption of BBB integrity, evidenced by increased levels of exogenously administered sodium fluorescein in the striatum. Also, LPS exposure caused delayed impairment in social recognition memory (evaluated at day 38 after treatments) and increase in the striatal levels of 3-nitrotyrosine. These events were observed in the absence of significant changes in motor coordination and in the levels of tyrosine hydroxylase (TH) in the striatum and substantia nigra. PQ exposure, which caused a long-lasting decrease of striatal mitochondrial complex I activity, did not modify LPS-induced behavioral and striatal biochemical changes. The results indicate that systemic administration of LPS causes delayed social recognition memory deficit and striatal nitrosative stress in adult mice and that the coexposure to a moderately toxic dose of PQ did not magnify these events. In addition, PQ-induced inhibition of striatal mitochondrial complex I was also not magnified by LPS exposure, indicating the absence of synergic neurotoxic effects of LPS and PQ in this experimental model.

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Acknowledgements

The authors gratefully thank the financial support and grants provided by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (especially project 300966/2014-8) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Correspondence to CinaraLudvig Gonçalves or Marcelo Farina.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Gonçalves, C., dos Santos, D.B., Portilho, S.S. et al. Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social Recognition Memory Are Not Magnified by Paraquat Coexposure. Neurochem Res 43, 745–759 (2018). https://doi.org/10.1007/s11064-018-2477-z

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Keywords

  • Lipopolysaccharide
  • Paraquat
  • Neurotoxicity
  • blood–brain barrier
  • Social recognition memory
  • Striatum