CMV Infection Attenuates the Disease Course in a Murine Model of Multiple Sclerosis

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies

Reduced Cortisol and Metabolic Responses of Thin Ewes to an Acute Cold Challenge in Mid-Pregnancy: Implications for Animal Physiology and Welfare

Background: Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal’s ability to cope with cold challenges. Methods: Eighteen pregnant ewes with a BCS of 2.760.1 were fed to attain low (LBC: BCS2.360.1), medium (MBC: BCS3.260.2) or high BCS (HBC: BCS3.660.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.460.1uC) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. Results: During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P,0.01, P,0.01 and P,0.05, respectively) and HBC ewes (P,0.05, P,0.01 and P,0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P,0.05) and HBC ewes (P,0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P,0.05 and P,0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P,0.01). Glucose concentrations and internal body temperature (Tcore) increased in all treatments, although peak Tcore tended to be higher in HBC ewes (P,0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P,0.05). Conclusion: Even though all ewes were able to increase Tcore and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced

Psychosocial Stress, Cortisol Levels, and Maintenance of Vaginal Health

Stress stimuli are ubiquitous and women do not enjoy any exemptions. The physiologic “fight-or-flight” response may be deleterious to the female lower genital tract microbiome if the stress stimuli persist for longer than necessary. Persistent exposure to psychosocial stress and stimulation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes, and associated hormones are risk factors for several infections including genitourinary tract infections. Though this could be due to a dysregulated immune response, a cortisol-induced inhibition of vaginal glycogen deposition may be involved especially in the instance of vaginal infection. The estrogen-related increased vaginal glycogen and epithelial maturation are required for the maintenance of a healthy vaginal ecosystem (eubiosis). The ability of cortisol to disrupt this process as indicated in animal models is important in the pathogenesis of vaginal dysbiosis and the subsequent development of infection and inflammation. This phenomenon may be more crucial in pregnancy where a healthy Lactobacillus-dominated vaginal microbiota is sacrosanct, and there is local production of more corticotropin-releasing hormone (CRH) from the decidua, fetal membranes and placenta. To highlight the relationship between the stress hormone cortisol and the vaginal microbiomial architecture and function, the potential role of cortisol in the maintenance of vaginal health is examined

A community-sourced glossary of open scholarship terms

Supplementary Information: This list of terms represents the ‘Open Scholarship Glossary 1.0’ (available at: https://forrt.org/glossary/. Glossary available under a CC BY NC SA 4.0 license at: https://static-content.springer.com/esm/art%3A10.1038%2Fs41562-021-01269-4/MediaObjects/41562_2021_1269_MOESM1_ESM.pdf).https://static-content.springer.com/esm/art%3A10.1038%2Fs41562-021-01269-4/MediaObjects/41562_2021_1269_MOESM1_ESM.pd