Nurr1 reduction influences the onset of chronic EAE in mice
Francesca Montarolo1, Simona Perga2, Serena Martire2
1AOU 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@unito.it.
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.
Insights
Reduced Nurr1 (nuclear receptor 4A2) exacerbates experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. This suggests Nurr1 deficiency worsens early EAE onset and spinal cord inflammation.
Area of Science:
- Neuroimmunology
- Molecular Neuroscience
Background:
- Nurr1 (nuclear receptor 4A2) exhibits anti-inflammatory properties in glial cells.
- Down-regulation of Nurr1 in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients correlates with disease severity.
Purpose of the Study:
- To investigate the role of Nurr1 deficiency in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
- To assess the impact of reduced Nurr1 on disease onset, progression, and neuroinflammation.
Main Methods:
- EAE was induced in heterozygous Nurr1 knockout mice.
- Clinical neurological scores were monitored throughout the pre-symptomatic, acute, and chronic disease phases.
- Neuroinflammation and tissue damage were assessed in the spinal cord.
Main Results:
- Nurr1 deficiency led to an earlier onset of EAE.
- Increased inflammatory cell infiltration was observed in the spinal cords of Nurr1-deficient mice.
- The severity of neuroinflammation was exacerbated by the reduction of Nurr1.
Conclusions:
- A defect in Nurr1 function promotes early-onset EAE.
- Nurr1 plays a critical role in modulating the inflammatory response during the early stages of EAE.
- Targeting Nurr1 may offer therapeutic potential for mitigating early MS-like pathology.
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