The present study investigated the effects of social defeat stress on the behaviours and expressions of 78-kDa glucose-regulated protein (Grp78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and choline acetyltransferase (Chat) in the brains of adolescent mice. Adolescent male C57BL/6J mice were divided into two groups (susceptible and unsusceptible) after 10 d social defeat stress. In expt 1, behavioural tests were conducted and brains were processed for Western blotting on day 21 after stress. In expt 2, social avoidance tests were conducted and brains were subsequently processed for Western blotting on day 12 after stress. Chronic social defeat stress produced more pronounced depression-like behaviours such as decreased locomotion and social interaction, increased anxiety-like behaviours and immobility, and impaired memory performance in susceptible mice. Moreover, susceptible mice showed greater expression of Grp78 and CHOP in the amygdala (Amyg) on days 12 and 21 compared with the other groups. Susceptible and unsusceptible groups showed significant increases in Grp78 and CHOP expression in the prefrontal cortex (PFC) and hippocampus (Hipp) on day 12 compared with the control group; this persisted until day 21. The levels of Chat measured on days 12 and 21 were significantly lower in the PFC, Amyg and Hipp of all defeated mice compared with controls. The findings of the behavioural tests indicate that chronic social defeat in adolescents produces anxiety-like behaviours, social withdrawal, despair-like behaviours and cognitive impairment. The Grp78, CHOP and Chat results suggest that the selective response of endoplasmic reticulum stress proteins in the Amyg plays an important role in the vulnerability-stress model of depression.

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.

No abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a massive impact on human lives worldwide. While the airborne SARS-CoV-2 primarily affects the lungs, viremia is not uncommon. As placental trophoblasts are directly bathed in maternal blood, they are vulnerable to SARS-CoV-2. Intriguingly, the human fetus is largely spared from SARS-CoV-2 infection. We tested whether the human placenta expresses the main SARS-CoV-2 entry factors angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin and showed that ACE2 and TMPRSS2 are expressed in the trophoblast rather than in other placental villous cells. While furin is expressed in the main placental villous cell types, we surveyed, trophoblasts exhibit the highest expression. In line with the expression of these entry factors, we demonstrated that a SARS-CoV-2 pseudovirus could enter primary human trophoblasts. Mechanisms underlying placental defense against SARS-CoV-2 infection likely involve postentry processing, which may be germane for mitigating interventions against SARS-CoV-2. IMPORTANCE Pregnant women worldwide have been affected by COVID-19. As the virus is commonly spread to various organs via the bloodstream and because human placental trophoblasts are directly bathed in maternal blood, feto-placental infection by SARS-CoV-2 seems likely. However, despite the heightened risk to pregnant women, thus far the transmission risk of COVID-19 to the feto-placental unit seems extremely low. This has been recently attributed to a negligible expression of SARS-CoV-2 entry factors in the human placenta. We therefore sought to explore the expression of the entry factors ACE2 and TMPRSS2 in the different cell types of human placental villi. Using a combination of transcriptome sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), in situ hybridization, and immunofluorescence, we found that trophoblasts, but not the other main villous cell types, express ACE2 and TMPRSS2, with a broad expression of furin. Correspondingly, we also showed that primary human trophoblasts are permissive to entry of SARS-CoV-2 pseudovirus particles.

The present study demonstrated that chronic social defeat stress in mice produces stress-related behaviors. Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time-course effects.

Lifetime suicidal behavior was highly prevalent in Jeollabuk-do Province. The most significant risk factors were found to be social support, family disharmony, anger, depression, and low self-esteem in Koreans.

BackgroundChronic social defeat stress induces depression and anxiety-like behaviors in rodents and also responsible for differentiating defeated animals into stress susceptible and resilient groups. The present study investigated the effects of social defeat stress on a variety of behavioral parameters like social behavior, spatial learning and memory and anxiety like behaviors. Additionally, the levels of various dopaminergic markers, including the long and short form of the D2 receptor, and total and phosphorylated dopamine and cyclic adenosine 3′,5′-monophosphate regulated phosphoprotein-32, and proteins involved in intracellular trafficking were assessed in several key brain regions in young adult mice.MethodsMouse model of chronic social defeat was established by resident-intruder paradigm, and to evaluate the effect of chronic social defeat, mice were subjected to behavioral tests like spontaneous locomotor activity, elevated plus maze (EPM), social interaction and Morris water maze tests.ResultsMice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. The susceptible group exhibited greater decreases in time spent in the open and closed arms compared to the control group on the EPM. In the social interaction test, the susceptible group showed greater increases in submissive and neutral behaviors and greater decreases in social behaviors relative to baseline compared to the control group. Furthermore, increased expression of D2L, D2S, Rab4, and G protein-coupled receptor associated sorting protein-1 was observed in the amygdala of the susceptible group compared to the control group.ConclusionThese findings suggest that social defeat stress induce anxiety-like and altered social interacting behaviors, and changes in dopaminergic markers and intracellular trafficking-related proteins.Electronic supplementary materialThe online version of this article (10.1186/s12993-018-0148-5) contains supplementary material, which is available to authorized users.

Exposing adrenal chromaffin cells to 5 ns electric pulses (nsPEF) causes a rapid rise in intracellular Ca2+ ([Ca2+]i) that is solely the result of Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). This study explored the effect of longer duration nsPEF on [Ca2+]i. Single 150, 200, or 400 ns pulses at 3.1 kV/cm evoked rapid increases in [Ca2+]i, the magnitude of which increased linearly with pulse width and electric field amplitude. Recovery of [Ca2+]i to prestimulus levels was faster for 150 ns exposures. Regardless of pulse width, no rise in [Ca2+]i occurred in the absence of extracellular Ca2+, indicating that the source of Ca2+ was from outside the cell. Ca2+ responses evoked by a 150 ns pulse were inhibited to varying degrees by ω-agatoxin IVA, ω-conotoxin GVIA, nitrendipine or nimodipine, antagonists of P/Q-, N-, and L-type VGCCs, respectively, and by 67% when all four types of VGCCs were blocked simultaneously. The remaining Ca2+ influx insensitive to VGCC inhibitors was attributed to plasma membrane nanoporation, which comprised the E-field sensitive component of the response. Both pathways of Ca2+ entry were inhibited by 200 μM Cd2+. These results demonstrate that, in excitable chromaffin cells, single 150–400 ns pulses increased the permeability of the plasma membrane to Ca2+ in addition to causing Ca2+ influx via VGCCs.