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Nurr1 reduction influences the onset of chronic EAE in mice

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Abstract

Objective

Nurr1 plays anti-inflammatory functions in astrocytes/microglia. Gene expression analysis reveals Nurr1 down-regulation in PBMCs of MS patients that negatively correlates with disease aggressiveness. This study assesses the consequences of Nurr1 reduction in a MS model represented by EAE.

Methods

EAE was induced in heterozygous Nurr1 knockout mice. Clinical course was evaluated during pre-symptomatic, acute, and chronic phases. Neurohistopathological state was analyzed in spinal cord.

Results and conclusions

Nurr1 defect induces early EAE onset and increases inflammatory infiltrates in spinal cord suggesting a Nurr1 role in the early phase of EAE.

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References

  1. Saijo K, Winner B, Carson C, et al. A Nurr1/CoREST pathway in microglia/astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137:47–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Achiron A, Grotto I, Balicer R, et al. Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of MS. Neurobiol Dis. 2011;38(2):201–9.

    Article  Google Scholar 

  3. Satoh J, Nakanishi M, Koike F, et al. Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in MS. Neurobiol Dis. 2005;18(3):537–50.

    Article  CAS  PubMed  Google Scholar 

  4. Wang Z, Benoit G, Liu J, et al. Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature. 2003;423(6939):555–60.

    Article  CAS  PubMed  Google Scholar 

  5. Sekiya T, Kashiwagi I, Yoshida R, et al. Nr4a receptors are essential for thymic regulatory T-cell development and immune homeostasis. Nat Immunol. 2013;14:230–7.

    Article  CAS  PubMed  Google Scholar 

  6. Gilli F, Lindberg RLP, Valentino P, et al. Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with MS. Plos One. 2010;5(1):e8962.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Gilli F, Navone ND, Perga S, et al. Loss of braking signals during inflammation: a factor affecting the development and disease course of MS. Arch Neurol. 2011;68(7):879–88.

    Article  PubMed  Google Scholar 

  8. Navone ND, Perga S, Martire S, et al. Monocytes and CD4+ T-cells contribution to the under-expression of NR4A2 and TNFAIP3 genes in patients with MS. J Neuroimmunol. 2014;272(1–2):99102.

    Google Scholar 

  9. Montarolo F, Raffaele C, Perga S, et al. Effects of IP7e, a potent activator of the Nurr1 signaling pathway, on EAE in mice. PloS One. 2014;9(9):e108791.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, et al. Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA. 1998;95(7):4013–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Raveney BJ, Oki S, Yamamura T. Nuclear receptor NR4A2 orchestrates Th17 cell-mediated autoimmune inflammation via IL-21 signalling. PloS One. 2013;8(2):e56595.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The Nurr1-KO mice were originally from the laboratory of Prof. O. M. Conneely (Baylor College Medicine, Houston, USA). The work was supported by the Fondazione Italiana Sclerosi Multipla (FISM 2010/R/7).

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Authors and Affiliations

  1. AOU San Luigi Gonzaga, Neurobiology Unit, Neurologia 2, CReSM (Regional Referring Center of Multiple Sclerosis) and Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, 10, 10043, Orbassano, TO, Italy

    Francesca Montarolo, Simona Perga, Serena Martire & Antonio Bertolotto

Authors
  1. Francesca Montarolo
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  2. Simona Perga
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  3. Serena Martire
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  4. Antonio Bertolotto
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Corresponding author

Correspondence to Francesca Montarolo.

Additional information

Responsible Editor: John Di Battista.

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Montarolo, F., Perga, S., Martire, S. et al. Nurr1 reduction influences the onset of chronic EAE in mice. Inflamm. Res. 64, 841–844 (2015). https://doi.org/10.1007/s00011-015-0871-4

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  • DOI: https://doi.org/10.1007/s00011-015-0871-4

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