The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior

Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

Marketer as a Barbie Game Changer

This paper addresses issues about how the Barbie doll can provide an unrealistic vision of how women should look and what marketers can do about it. Barbie is a well-known doll that has become a role model for girls. However, Barbie dolls have attracted much criticism. Studies found that Barbie shapes the body image of young girls and possibly creates body dissatisfaction and low self-esteem among girls. Body dissatisfaction can lead to eating disorders and low self-esteem can lead to depressive behavior. Answering that phenomenon, Barbie launched Barbie Fashionista that has a diverse body type. However, Girls still tend to choose thinner Barbie. Barbie’s marketer should encourage girls to play more with a more realistic body image Barbie such as curvy, tall, and petite, and encourage the children to feel good about their bodies.

Extracellular vesicles from Gram-positive and Gram-negative probiotics remediate stress-induced depressive behavior in mice

Chronic stress causes maladaptive changes in the brain that lead to depressive behavior. In the present study, we investigate whether chronic stress alters gut microbiota and whether specific mediators of probiotics remedies stress-induced maladaptive changes in the brain. Mice treated with daily 2-h restraint for 14 days (CRST) exhibit depressive-like behavior. Sequence readings of 16S rRNA genes prepared from fecal samples taken from CRST-treated mice suggest that chronic stress induces gut microbiota changes that are pronounced 14 days after the last restraint, relative to those that occur in the 14-day stress phase. The genus Lactobacillus is one such microbiota substantially changed following chronic stress. In contrast, post-stress treatment with extracellular vesicles (EVs) derived from the Gram-positive probiotic Lactobacillus plantarum are sufficient to ameliorate stress-induced depressive-like behavior. Interestingly, EVs from the Gram-positive probiotic Bacillus subtilis and EVs from the Gram-negative probiotic Akkermansia muciniphila also produce anti-depressive-like effects. While chronic stress decreases expression of MeCP2, Sirt1, and/or neurotrophic factors in the hippocampus, EVs from the selected probiotics differentially restore stress-induced changes of these factors. These results suggest that chronic stress produces persistent changes in gut microbiota composition, whereas EVs of certain probiotics can be used for treatment of stress-induced maladaptive changes.