Contributions
Abstract: EP1495
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease in which inflammation exerts a key pathophysiological role. Recently, we reported a down-regulation of the anti-inflammatory NUclear receptor related protein 1 (Nurr1, also called NR4A2) gene expression level in blood of treatment-naïve relapsing-remitting MS (RRMS) patients as compared to healthy controls (HC). Notably, we observed the abnormal expression levels of NR4A2 being reverted in MS patients during pregnancy, which represents a transitory state of immune tolerance associated with reduced disease activity. The transcription factor NR4A2 belongs to the steroid nuclear hormone receptor subfamily 4, group A (NR4A), which includes NR4A1 and NR4A3 as well. The three members of the NR4A family share a high degree of homology and a common structure, particularly in their DNA-binding-domain, which may give rise to functional compensation mechanisms. Several evidences report a neuro-protective function of the NR4A exerted through the inhibition of the pro-inflammatory transcription factor NF-kB in microglia and astrocytes.
Objective and aims: Based on the evidence that systemic inflammation induces cell infiltration into the brain parenchyma enhancing the central nervous system (CNS) damage, we characterized NR4A expression in human HC and MS blood samples and brain cryo-sections.
Methods: Gene expression levels of NR4A were evaluated by RT Real time PCR analysis. Demographical and clinical parameters were correlated to the expression level.
Results: First, gene expression levels of NR4A are down-regulated in whole blood obtained from treatment-naïve RRMS patient compared to HC. Second, moving into the CNS, we observed that NR4A1, NR4A2 and NR4A3 are expressed in WM and in GM of HC as well as in normal appearing WM (NAGM) and normal appearing GM (NAGM) of MS patients. Furthermore, we reported a reduction of the NR4A1 and NR4A2 transcripts in GM lesions in comparison to their relative NAGM. On the contrary, the NR4A resulted not modulated in WM lesions in comparison to their relative NAWM.
Conclusions: The present results refer to a defect of the NR4A in blood and damaged brain samples obtained from MS subjects.
Disclosure: Francesca Montarolo: nothing to disclose
Simona Perga: nothing to disclose
Serena Martire: nothing to disclose
Gabriele Bono: nothing to disclose
Jessica Bertolo nothing to disclose
Antonio Bertolotto: nothing to disclose
Abstract: EP1495
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease in which inflammation exerts a key pathophysiological role. Recently, we reported a down-regulation of the anti-inflammatory NUclear receptor related protein 1 (Nurr1, also called NR4A2) gene expression level in blood of treatment-naïve relapsing-remitting MS (RRMS) patients as compared to healthy controls (HC). Notably, we observed the abnormal expression levels of NR4A2 being reverted in MS patients during pregnancy, which represents a transitory state of immune tolerance associated with reduced disease activity. The transcription factor NR4A2 belongs to the steroid nuclear hormone receptor subfamily 4, group A (NR4A), which includes NR4A1 and NR4A3 as well. The three members of the NR4A family share a high degree of homology and a common structure, particularly in their DNA-binding-domain, which may give rise to functional compensation mechanisms. Several evidences report a neuro-protective function of the NR4A exerted through the inhibition of the pro-inflammatory transcription factor NF-kB in microglia and astrocytes.
Objective and aims: Based on the evidence that systemic inflammation induces cell infiltration into the brain parenchyma enhancing the central nervous system (CNS) damage, we characterized NR4A expression in human HC and MS blood samples and brain cryo-sections.
Methods: Gene expression levels of NR4A were evaluated by RT Real time PCR analysis. Demographical and clinical parameters were correlated to the expression level.
Results: First, gene expression levels of NR4A are down-regulated in whole blood obtained from treatment-naïve RRMS patient compared to HC. Second, moving into the CNS, we observed that NR4A1, NR4A2 and NR4A3 are expressed in WM and in GM of HC as well as in normal appearing WM (NAGM) and normal appearing GM (NAGM) of MS patients. Furthermore, we reported a reduction of the NR4A1 and NR4A2 transcripts in GM lesions in comparison to their relative NAGM. On the contrary, the NR4A resulted not modulated in WM lesions in comparison to their relative NAWM.
Conclusions: The present results refer to a defect of the NR4A in blood and damaged brain samples obtained from MS subjects.
Disclosure: Francesca Montarolo: nothing to disclose
Simona Perga: nothing to disclose
Serena Martire: nothing to disclose
Gabriele Bono: nothing to disclose
Jessica Bertolo nothing to disclose
Antonio Bertolotto: nothing to disclose