Neuroscience
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There is growing basic and clinical evidence that major depressive disorder (MDD) is associated with gut microbiome alterations, but clinical studies have tended not to adjust for confounding factors. And few studies on the gut microbiome focused on young adults with MDD. Here we performed a pilot study to compare the gut microbiome of young adults with MDD with healthy controls. ⋯ Abundance of Sutterellaceae and species belonging to Clostridium, Eubacterium, and Ruminococcus were significantly different between groups. The cysteine degradation I pathway was increased in MDD. After controlling for most confounding factors, this pilot study provides new evidence on the specific, often subtle gut dysbiosis affecting young adults with depression.
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The nonapeptide system modulates a diversity of social behaviors, including aggression, parental care, affiliation, sexual behavior, and pair bonding. Such social behaviors are regulated through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin V1a receptor (AVPR1A) in the brain. Nonapeptide receptor distributions have been mapped for several species, however, studies have demonstrated that there is substantial variation across species. ⋯ Here we conducted receptor autoradiography to map distributions of OXTR and AVPR1A binding throughout the basal forebrain and midbrain of female and male Mongolian gerbils. Further, we assessed whether gonadal sex influenced binding densities in brain regions important for social behavior and reward, however, we observed no effects of sex on OXTR or AVPR1A binding densities. These findings provide mapping distributions of nonapeptide receptors in male and female Mongolian gerbils, laying a foundation for future studies that seek to manipulate the nonapeptide system to examine nonapeptide-mediated social behavior.
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Inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) is an intracellular Ca2+ release channel important for a number of fundamental cellular functions. Consistent with its critical physiological significance, mutations in ITPR1 are associated with disease. Surprisingly, nearly all the disease-associated ITPR1 mutations characterized to date are loss of function. ⋯ On the other hand, ITPR1-D2594K+/- mice exhibited increased sensitivity to thermal and mechanical stimulation compared to WT. Interestingly, R-carvedilol treatment attenuated the enhanced thermal and mechanical nociception in ITPR1-D2594K+/- mice. Thus, the ITPR1-D2594K+/- mutation in the channel's gating domain has a marked impact on motor movements and pain perception, but little effect on hippocampal learning and memory.
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Mesenchymal stem cells (MSCs)-derived exosomes are demonstrated to exert neuroprotective effects in stroke. We aimed to explore the role and mechanism of long non-coding RNA (lncRNA) KLF3 antisense RNA 1 (KLF3-AS1) in bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) in cerebral ischemia/reperfusion (I/R) injury. Exosomes were isolated from the culture medium of BMSCs. ⋯ KLF3-AS1 was found to recruit ETS variant transcription factor 4 (ETV4), which upregulated Sirt1 expression. Knockdown of KLF3-AS1 neutralized the protective effects of BMSCs-Exos on MCAO-induced brain injury, which was then reversed by the treatment with Sirt1 inhibitor EX527. We concluded that KLF3-AS1 derived from BMSCs-Exos promoted autophagy to alleviate I/R injury via ETV4/Sirt1 axis.