An extended association screen in multiple sclerosis using 202 microsatellite markers targeting apoptosis-related genes does not reveal new predisposing factors

Apoptosis, the programmed death of cells, plays a distinct role in the etiopathogenesis of Multiple sclerosis (MS), a common disease of the central nervous system with complex genetic background. Yet, it is not clear whether the impact of apoptosis is due to altered apoptotic behaviour caused by variations of apoptosis-related genes. Instead, apoptosis in MS may also represent a secondary response to cellular stress during acute inflammation in the central nervous system. Here, we screened 202 apoptosis-related genes for association by genotyping 202 microsatellite markers in initially 160 MS patients and 160 controls, both divided in 4 sets of pooled DNA samples, respectively. When applying Bonferroni correction, no significant differences in allele frequencies were detected between MS patients and controls. Nevertheless, we chose 7 markers for retyping in individual DNA samples, thereby eliminating 6 markers from the list of candidates. The remaining candidate, the ERBB3 gene microsatellite, was genotyped in additional 245 MS patients and controls. No association of the ERBB3 marker with the disease was detected in these additional cohorts. In consequence, we did not find further evidence for apoptosis-related genes as predisposition factors in MS

Immunosuppressive potential of human amnion epithelial cells in the treatment of experimental autoimmune encephalomyelitis

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). In recent years, it has been found that cells such as human amnion epithelial cells (hAECs) have the ability to modulate immune responses in vitro and in vivo and can differentiate into multiple cell lineages. Accordingly, we investigated the immunoregulatory effects of hAECs as a potential therapy in an MS-like disease, EAE (experimental autoimmune encephalomyelitis), in mice. METHODS: Using flow cytometry, the phenotypic profile of hAECs from different donors was assessed. The immunomodulatory properties of hAECs were examined in vitro using antigen-specific and one-way mixed lymphocyte proliferation assays. The therapeutic efficacy of hAECs was examined using a relapsing-remitting model of EAE in NOD/Lt mice. T cell responsiveness, cytokine secretion, T regulatory, and T helper cell phenotype were determined in the peripheral lymphoid organs and CNS of these animals. RESULTS: In vitro, hAECs suppressed both specific and non-specific T cell proliferation, decreased pro-inflammatory cytokine production, and inhibited the activation of stimulated T cells. Furthermore, T cells retained their naïve phenotype when co-cultured with hAECs. In vivo studies revealed that hAECs not only suppressed the development of EAE but also prevented disease relapse in these mice. T cell responses and production of the pro-inflammatory cytokine interleukin (IL)-17A were reduced in hAEC-treated mice, and this was coupled with a significant increase in the number of peripheral T regulatory cells and naïve CD4+ T cells. Furthermore, increased proportions of Th2 cells in the peripheral lymphoid organs and within the CNS were observed. CONCLUSION: The therapeutic effect of hAECs is in part mediated by inducing an anti-inflammatory response within the CNS, demonstrating that hAECs hold promise for the treatment of autoimmune diseases like MS

The prevalence of psychiatric symptoms before the diagnosis of Parkinson's disease in a nationwide cohort: A comparison to patients with cerebral infarction

Objectives Psychiatric symptoms (PS) can be non-motor features in Parkinson's disease (PD) which are common even in the prodromal, untreated phase of the disease. Some PS, especially depression and anxiety recently became known predictive markers for PD. Our objective was to explore retrospectively the prevalence of PS before the diagnosis of PD. Methods In the framework of the Hungarian Brain Research Program we created a database from medical and medication reports submitted for reimbursement purposes to the National Health Insurance Fund in Hungary, a country with 10 million inhabitants and a single payer health insurance system. We used record linkage to evaluate the prevalence of PS before the diagnosis of PD and compared that with patients with ischemic cerebrovascular lesion (ICL) in the period between 2004-2016 using ICD-10 codes of G20 for PD, I63-64 for ICL and F00-F99 for PS. We included only those patients who got their PD, ICL and psychiatric diagnosis at least twice. Results There were 79 795 patients with PD and 676 874 patients with ICL. Of the PD patients 16% whereas of those with ischemic cerebrovascular lesion 9.7% had a psychiatric diagnosis before the first appearance of PD or ICL (p<0.001) established in psychiatric care at least twice. The higher rate of PS in PD compared to ICL remained significant after controlling for age and gender in logistic regression analysis. The difference between PD and ICL was significant for Mood disorders (F30-F39), Organic, including symptomatic, mental disorders (F00-F09), Neurotic, stress-related and somatoform disorders (F40-F48) and Schizophrenia, schizotypal and delusional disorders (F20-F29) diagnosis categories (p<0.001, for all). Discussion The higher rate of psychiatric morbidity in the premotor phase of PD may reflect neurotransmitter changes in the early phase of PD