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Mild Hyperhomocysteinemia Increases Brain Acetylcholinesterase and Proinflammatory Cytokine Levels in Different Tissues

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Abstract

Mild hyperhomocysteinemia is considered to be a risk factor for cerebral and cardiovascular disorders and can be modeled in experimental rats. Inflammation has been implicated in the toxic effects of homocysteine. Cholinergic signaling controls cytokine production and inflammation through the “cholinergic anti-inflammatory pathway,” and brain acetylcholinesterase activity plays a role in this regulation. The aim of this present study is to investigate the effect of mild chronic hyperhomocysteinemia on proinflammatory cytokine levels in the brain, heart, and serum of rats. Activity, immunocontent, and gene expression of acetylcholinesterase in the brain and butyrylcholinesterase activity in serum were also evaluated. Mild hyperhomocysteinemia was induced in Wistar rats by homocysteine administration (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th days of life. Controls received saline in the same volumes. Results demonstrated an increase in tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and the chemokine monocyte chemotactic protein-1 (MCP-1) in the hippocampus, as well as an increase in IL-1β and IL-6 levels in cerebral cortex. Acetylcholinesterase activity was increased in rats subjected to mild hyperhomocysteinemia in both cerebral structures tested; the immunocontent of this enzyme was also increased in the cerebral cortex and decreased in the hippocampus. Levels of acetylcholinesterase mRNA transcripts were not altered. Peripherally, homocysteine increased TNF-α, IL-6, and MCP-1 levels in the heart and IL-6 levels in serum. Taken altogether, these findings suggest that homocysteine promotes an inflammatory status that can contribute, at least in part, to neuronal and cardiovascular dysfunctions observed in mild hyperhomocysteinemia.

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Acknowledgments

This work was supported in part by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil).

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Authors and Affiliations

  1. Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Emilene B. S. Scherer, Samanta O. Loureiro, Fernanda C. Vuaden, Aline A. da Cunha, Felipe Schmitz, Janaína Kolling, Luiz Eduardo B. Savio & Angela T. S. Wyse

  2. Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Maurício R. Bogo & Carla D. Bonan

  3. Laboratório de Isquemia Cerebral e Psicobiologia dos Transtornos Mentais, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carlos A. Netto

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  1. Emilene B. S. Scherer
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  2. Samanta O. Loureiro
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  3. Fernanda C. Vuaden
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  4. Aline A. da Cunha
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Correspondence to Angela T. S. Wyse.

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Scherer, E.B.S., Loureiro, S.O., Vuaden, F.C. et al. Mild Hyperhomocysteinemia Increases Brain Acetylcholinesterase and Proinflammatory Cytokine Levels in Different Tissues. Mol Neurobiol 50, 589–596 (2014). https://doi.org/10.1007/s12035-014-8660-6

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