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Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, biological mechanisms of their effects and timing-effects, is still limited. Both PM2.5and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development across several domains, including bio-behavioral, cognitive and socio-emotional domains. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5on SLC6A4 DNAmlevels in newborns. Mother–infant dyads (N= 307) were enrolled at delivery during the COVID-19 pandemic. Infants’ methylation status was assessed in 13 CpG sites within the SLC6A4gene’s region (chr17:28562750–28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5exposure throughout the entire gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Among several potentially confounding socio-demographic and health-related factors, infant’s sex was significantly associated with infants’ SLC6A4 DNAm levels, thus hierarchical regression models were adjusted for infant’s sex. Higher levels of SLC6A4 DNAmat 6 CpG sites were found in newborns born to mothers reporting higher levels of antenatal PRS and greater PM2.5exposure across gestation, while adjusting for infant’s sex. These effects were especially evident when exposure to elevated PM2.5occurred during the second trimester of pregnancy. Several important brain processes (e.g., synaptogenesis and myelination) occur during mid-pregnancy, potentially making the second trimester a sensitive time window for the effects of stress-related exposures. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.

•Disease modifying treatments potentially influence response to SARS-CoV-2 mRNA vaccines.•SARS-CoV-2 specific CD4+T cell responses to mRNA vaccines were high in MS patients on ocrelizumab and teriflunomide.•SARS-CoV-2 specific CD4+T cell responses to mRNA vaccines were largely impaired in patients on treatment with S1Pr-mod.•When present, SARS-CoV-2 specific T cells were mainly of Th1 type and stable over time and after booster vaccine doses.

ObjectiveTo study the effect of natural menopause on multiple sclerosis clinical course.MethodsThis was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.Results148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).ConclusionNatural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

•PM2.5, PM10 and NO2 are risk factors for Covid-19 pneumonia among MS patients.•We studied the joint exposure to the three pollutants as an environmental mixture.•The most dangerous pollutants within the mixture were NO2 and PM2.5.

•PBMCs from people with MS (PwMS) have lower HuR than healthy controls (HC).•PBMCs from PwMS have a lower MnSOD protein content compared to HC.•SOD2mRNA is a new target of HuR protein.•In PBMCs from PwMS one year of dimethyl fumarate restores HuR and MnSOD protein content to the HC's levels.

Coronavirus disease 2019 (COVID-19) raises particular concerns for people with multiple sclerosis (PwMS) on disease-modifying treatments (DMTs), and for physicians caring for them. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on PwMS receiving DMTs that inhibit immune cell trafficking, such as natalizumab (NTZ) and fingolimod (FTY), remains to be determined, as do the possible effects of these drugs on both the infection and the related disease.

•HuR, an ELAV-like protein, may be involved in MS pathogenesis.•HuR levels are lower in PBMCs from MS patients compared to healthy controls.•The HSP70-2rs1061581 polymorphism G allele is confirmed to be associated with MS.•MS pathology may disrupt the link between HuR and its target HSP70-2.

•BREMSO score predicts unfavourable course of MS at the onset of the disease.•BREMSO score can equate different cohorts of MS patients in real-world setting.•In a real-world setting, early treatment with im IFN-β1a confirmed a positive effect on MS course.

Neural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the CNS. Metabolites, such as succinate, modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here, we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage. Inflammatory MPs release succinate, which activates succinate receptor 1 (SUCNR1)/GPR91 on NSCs, leading them to secrete prostaglandin E2 and scavenge extracellular succinate with consequential anti-inflammatory effects. Thus, our work reveals an unexpected role for the succinate-SUCNR1 axis in somatic and directly induced NSCs, which controls the response of stem cells to inflammatory metabolic signals released by type 1 MPs in the chronically inflamed brain.