Revelation of the IFNα, IL-10, IL-8 and IL-1β as promising biomarkers reflecting immuno-pathological mechanisms in porcine Huntington's disease model

Valeková, Ivona; Jarkovská, Karla; Kotrcova, Eva; Bucci, John; Ellederová, Zdeňka; Juhás, Štefan; Gadher, Suresh Jivan; Kovářová, Hana

doi:10.1016/j.jneuroim.2016.02.012

Cited by 32 publications

(25 citation statements)

References 37 publications

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“…A transgenic porcine model, using fragments of human huntingtin protein, has been used as an animal model of HD. Elevated levels of IL-8 (and IL-1β) were found in transgenic animals [21] with activated microglia producing the increased levels of the chemokine. Since IL-8 was increased in serum, it was suggested that the chemokine could have utility as a biomarker for immunopathology in HD [22].…”

Section: Il-8 In Other Neurodegenerative Diseases Huntington's Diseasmentioning

confidence: 98%

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

McLarnon¹

2016

J Alzheimers Dis Parkinsonism

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Section: Il-8 In Other Neurodegenerative Diseases Huntington's Diseasmentioning

confidence: 98%

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

McLarnon¹

2016

J Alzheimers Dis Parkinsonism

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“…Primary glia cells including microglia, isolated from R6/2 transgenic mouse model, showed that iNOS, IL-1β, IL-6, and TNF-α were significantly elevated after LPS treatment (Hsiao et al, 2014), and IL-6 was increased in the microglia of R6/2 mouse brain (Bjorkqvist et al, 2008). In addition, higher levels of IL-1β and IL-8 were secreted by microglia in HD transgenic porcine model (Valekova et al, 2016). Furthermore, pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α were elevated both centrally (in the striatum and cerebrospinal fluid) and peripherally (in the plasma) in HD patients (Bjorkqvist et al, 2008; Chang et al, 2015; Rodrigues et al, 2016).…”

Section: Implication Of Functional Phenotypes Of Microglia In Hdmentioning

confidence: 99%

Microglial Activation in the Pathogenesis of Huntington’s Disease

Yang

Huang

et al. 2017

Front. Aging Neurosci.

100

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Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of HTT gene that encodes huntingtin protein. Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.

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“…CSF can reflect optimal changes in the brain tissue, leading us to use it as a source of biomarkers. We found decreased levels of IFNα and IL-10 in CSF and microglia secretome and increased levels of IL-8 and IL-1β only in microglial secretome in TgHD compared to WT controls [44]. Increased levels of IL-8 and IL-1β in plasma were also found in premanifest HD gene carriers and were correlated with increased central microglial activation [45].…”

Section: Discussionmentioning

confidence: 99%

Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age

et al. 2018

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Background: Huntington disease (HD) is an incurable neurodegenerative disease caused by the expansion of a polyglutamine sequence in a gene encoding the huntingtin (Htt) protein, which is expressed in almost all cells of the body. In addition to small animal models, new therapeutic approaches (including gene therapy) require large animal models as their large brains are a more realistic model for translational research. Objective: In this study, we describe phenotype development in transgenic minipigs (TgHD) expressing the N-terminal part of mutated human Htt at the age of 24 months. Methods: TgHD and wild-type littermates were compared. Western blot analysis and subcellular fractionation of different tissues was used to determine the fragmentation of Htt. Immunohistochemistry and optical analysis of coronal sections measuring aggregates, Htt expression, neuroinflammation, and myelination was applied. Furthermore, the expression of Golgi protein acyl-CoA binding domain containing 3 (ACBD3) was analyzed. Results: We found age-correlated Htt fragmentation in the brain. Among various tissues studied, the testes displayed the highest fragmentation, with Htt fragments detectable even in cell nuclei. Also, Golgi protein ACBD3 was upregulated in testes, which is in agreement with previously reported testicular degeneration in TgHD minipigs. Nevertheless, the TgHD-specific mutated Htt fragments were also present in the cytoplasm of striatum and cortex cells. Moreover, microglial cells were activated and myelination was slightly decreased, suggesting the development of a premanifest stage of neurodegeneration in TgHD minipigs. Conclusions: The gradual development of a neurodegenerative phenotype, accompanied with testicular degeneration, is observed in 24- month-old TgHD minipigs.

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Revelation of the IFNα, IL-10, IL-8 and IL-1β as promising biomarkers reflecting immuno-pathological mechanisms in porcine Huntington's disease model

Cited by 32 publications

References 37 publications

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

Microglial Activation in the Pathogenesis of Huntington’s Disease

Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age

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