Multiple sclerosis (MS) is an immune-mediated, demyelinating and neurodegenerative disease of the central nervous system. After traumatic brain injury, it is the leading cause of neurology disability in young adults. Considerable advances have been made in identifying genes involved in MS but the genetic and phenotypic complexity associated with this disease significantly hinders any progress. A novel class of small RNA molecules, microRNAs (miRNAs) has acquired much attention because they regulate the expression of up to 30% of protein-coding genes and may play a pivotal role in the development of many, if not all, complex diseases. Seven published studies investigated miRNAs from peripheral blood mononuclear cells, CD4+, CD8+ T cell, B lymphocytes, peripheral blood leukocytes, whole blood and brain astrocytes with MS risk. The absence of MS studies investigating plasma miRNA prompted the current investigation of identifying a circulating miRNA signature in MS. We conducted a microarray analysis of over 900 known miRNA transcripts from plasma samples collected from four MS individuals and four sex-aged and ethnicity matched healthy controls. We identified six plasma miRNA (miR-614, miR-572, miR-648, miR-1826, miR-422a and miR-22) that were significantly up-regulated and one plasma miRNA (miR-1979) that was significantly down-regulated in MS individuals. Both miR-422a and miR-22 have previously been implicated in MS. The present study is the first to show a circulating miRNA signature involved in MS that could serve as a potential prognostic and diagnostic biomarker for MS.

Objective: To assess the potential relationship of ultraviolet B radiation (UVB) and Epstein-Barr virus (EBV) exposure in explaining the period prevalence of multiple sclerosis (MS) in England. Methods: English national Hospital Episode Statistics covering all admissions to National HealthService hospitals in England in the 7 years from 1998 to 2005 were used to obtain the period prevalences of MS and infectious mononucleosis (IM) in England. The United States National Aeronautics and Space Administration's data on UVB intensity for England from the Nimbus 7 satellite was collected. The relationships among the 3 variables (MS prevalence, IM prevalence, and UVB intensity) were investigated. Results:The regression of MS against UVB intensity for all seasons had an r 2 of 0.61; when including the interaction of IM with seasonal UVB, the r 2 rose to 0.72. Conclusions:UVB exposure and IM together can explain a substantial proportion of the variance of MS. The effect of UVB on generating vitamin D seems the most likely candidate for explaining its relationship with MS. There is a pressing need to investigate the role of vitamin D and EBV and how they might interact to influence MS risk to identify potential prevention strategies. Multiple sclerosis (MS) is the most common disease of the CNS in young adults of Northern European descent. 1 MS seems unlikely to result from a single causative event; instead, the disease seems to develop in genetically susceptible populations as a result of environmental exposures. 2The most striking illustration of the importance of the environment in MS is its geographical distribution.3 Within regions of temperate climate, MS incidence and prevalence are thought to increase with latitude.3,4 The latitudinal trend starts around 42 degrees of latitude North.5 A cutoff at this latitude implicates solar wavelengths in the shorter UV range (ultraviolet B [UVB]) as UVB is strongly affected by the solar zenith angle.6 There is also a month of birth effect for MS, 7 which is also indicative of solar-correlated processes, and this effect is itself strongly latitude-dependent.We have recently reported period prevalence values for MS across England. 8 Epstein-Barr virus (EBV) is a B-lymphotropic human DNA herpesvirus that infects most individuals asymptomatically but in some people causes infectious mononucleosis (IM) upon infection.9 Because the risk of MS is increased in individuals with a clinical history of IM, [10][11][12] we also compared the geography of MS with the distribution of IM, and observed a strong correlation, but this was From the

Objective Exposure to early-life adversity (ELA) can result in long-term changes to physiological systems, which predispose individuals to negative health outcomes. This biological embedding of stress-responsive systems may operate via dysregulation of physiological resources in response to common stressors. The present pilot study outlines a novel experimental design to test how young adults' exposure to ELA influences neuroendocrine and inflammatory responses to acute stress. Materials and methods Participants were 12 males (mean age = 21.25), half of whom endorsed at least three significant adverse events up to age 18 years ('ELA group'), and half who confirmed zero ('controls'). Using a randomized within-subjects, between-groups experimental design, we induced acute psychosocial stress (Trier Social Stress Test, TSST), and included a nostress control condition one week apart. During these sessions, we obtained repeated measurements of physiological reactivity, gene expression of the glucocorticoid receptor (NR3C1), and plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) over a 4-hour window post-test. Results In this pilot study, the ELA group evinced higher cortisol response and blunted NR3C1 gene expression in response to the TSST compared with controls, while no differences were observed in the no-stress condition. For pro-inflammatory cytokines, only IL-6 increased significantly in response to the TSST, with no differences between the two groups.

Early life adversity (ELA) is a risk factor for early onset morbidities and mortality, a relationship that may be driven in part by immune system dysregulation. One mechanism of dysregulation that has yet to be fully examined in the context of ELA is alterations to immune cell dynamics in response to acute stress. Using a within-person between-group experimental design, we investigated stress-induced changes in immune cell populations, and how these changes may be altered in individuals with a history of ELA. Participants were young adults ( N = 34, aged 18–25 years, 53% female, 47% with a history of ELA). Complete immune cell counts were measured at four time-points over a 5-hour window across two sessions (Trier Social Stress Test [TSST] vs. no-stress) separated by a week. Across all participants, total white blood cells increased over time ( F (3,84)=38.97, p < .001) with a greater increase in response to the TSST compared to the no-stress condition at 240 minutes post-test ( b = 0.43±.19; t (179)=2.22, p = .027). This pattern was mirrored by neutrophil counts. Lymphocyte counts were initially depressed by TSST exposure ( b = −205±.67; t (184)= −3.07, p = .002) but recovered above baseline. ELA status was associated with higher stress-induced immune cell counts, a difference likely driven by increases in neutrophils ( F (1,22)=4.45, p = .046). Overall, these results indicate differential immune cell dynamics in response to acute stress in individuals with a history of ELA. This points to altered immune system functioning in the context of stress, a finding that may be driving increased morbidity and mortality risk for ELA-exposed individuals.