Nurr1 reduction influences the onset of chronic EAE in mice
- 364 Downloads
- 3 Citations
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.
Keywords
Nurr1 Multiple sclerosis Experimental autoimmune encephalomyelitis InflammationNotes
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).
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.PubMedCentralCrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.PubMedCentralCrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.PubMedCentralCrossRefPubMedGoogle 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.PubMedCentralCrossRefPubMedGoogle 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.PubMedCentralCrossRefPubMedGoogle Scholar