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Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation

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Abstract

Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250–300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.

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Acknowledgements

This research was supported by grants from CNPq (FP). FP, TB, FD-P, and RSC are CNPq Research Fellows.

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Authors and Affiliations

  1. Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarão, SC, Brazil

    Lucinéia Gainski Danielski, Amanda Della Giustina, Mariana Pereira Goldim, Drielly Florentino, Khiany Mathias, Leandro Garbossa, Rosiane de Bona Schraiber, Ana Olívia Martins Laurentino, Marina Goulart, Gislaine Tezza Rezin, Jucélia Jeremias Fortunato & Fabricia Petronilho

  2. Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil

    Monique Michels & Felipe Dal-Pizzol

  3. Laboratory of Neurogenomics, Research Center René Rachou/CPqRR, Oswaldo Cruz Foundation, Minas Gerais, Belo Horizonte, MG, Brazil

    Karina Barbosa de Queiroz, Markus Kohlhof & Roney S. Coimbra

  4. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA

    Joao Quevedo & Tatiana Barichello

  5. Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA

    Joao Quevedo & Tatiana Barichello

  6. Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA

    Joao Quevedo & Tatiana Barichello

  7. Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil

    Joao Quevedo & Tatiana Barichello

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  1. Lucinéia Gainski Danielski
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  2. Amanda Della Giustina
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Danielski, L.G., Giustina, A.D., Goldim, M.P. et al. Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation. Mol Neurobiol 55, 5255–5268 (2018). https://doi.org/10.1007/s12035-017-0706-0

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