Inflammatory changes in peripheral organs in the BACHD murine model of Huntington's disease

LIFE SCIENCES

卷:232

Article

Costa Valadao, Priscila Aparecida¹  Oliveira, Bruna da Silva¹  Joviano-Santos, Julliane V.¹  Marciano Vieira, Erica Leandro²  Rocha, Natalia Pessoa^2,3  Teixeira, Antonio Lucio³  Guatimosim, Cristina¹  de Miranda, Aline Silva^1,2 

[1] Univ Fed Minas Gerais, Dept Morfol, Belo Horizonte, MG, Brazil

[2] Univ Fed Minas Gerais, Fac Med, Lab Interdisciplinar Invest Med, Belo Horizonte, MG, Brazil

[3] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Neuropsychiat Program, McGovern Med Sch, Houston, TX 77030 USA

关键词: Huntington's disease;    Peripheral inflammation;    BACHD;    Cytokines;   

DOI  :  10.1016/j.lfs.2019.116653

来源: Elsevier

【 摘 要 】

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the gene encoding the huntingtin protein (HTT). This expansion leads to the formation of mutant huntingtin protein (mHTT) that is expressed in many body tissue cells. The mHTT interacts with several molecular pathways within different cell types, affecting the regulation of the immune system cells. It is still very limited the understanding of the immune changes in peripheral tissues in HD. Herein, we investigated the levels of inflammatory and regulatory cytokines in peripheral organs (i.e. kidney, heart, liver and spleen) of the 12-month-old BACHD model of HD. This robust murine model closely resembles the human disease. We found significant changes in cytokine levels in all organs analyzed. Increased levels of IL-6 were found in the kidney, while levels of IL-6 and IL-12p70 were increased in the heart of BACHD mice in comparison with wild-type (WT) animals. In the liver, we observed enhanced IL-12p70 and TNF-alpha levels. In the spleen, there was an increase in the levels of IL-4 and a decrease in the levels of IL-5 and IL-6 in BACHD compared to WT. Our findings provide the first evidence that the BACHD model also exhibits immune changes in peripheral organs, opening an avenue for the investigation of the potential role played by peripheral inflammatory response in HD. Further studies are needed to systematically address the mechanisms and pathways underlying immune signaling in peripheral organs in HD.

【 授权许可】

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