PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

[Research progress on the role of microglia in sepsis-associated encephalopathy].

Sepsis-associated encephalopathy (SAE) refers to diffuse brain dysfunction caused by sepsis, which is characterized by decreased attention, directional impairment, being prone to irritation, and in severe cases the patient will experience drowsiness and coma. The pathogenesis of SAE mainly includes neuroinflammation, damage of blood-brain barrier, cerebral vascular dysfunction, and neurometabolic changes, among which neuroinflammation is the core pathological process. Microglia are considered to be important immune cells of the central nervous system and play an important role in neuroinflammation. This article systematically describes the role of microglia in the development of SAE, and discusses the phenotype and related signaling pathways of microglia, in order to clarify the role of microglia in SAE and provide a theoretical basis for clinical treatment of SAE.

Anatomical study to the vessels of the lower limb by using CT scan and 3D reconstructions of the injected material.

PURPOSE: To find out the advantages and insufficiency of the 3D reconstruction and traditional anatomy by comparing them with each other. METHODS: 1. Infused with the radio-opaque material from the arteries and veins, respectively, fresh lower extremity specimens were subjected to spiral CT scanning and then 3D reconstruction was conducted to obtain 3D vessels. 2. Anatomizing the specimens to show the vessel system. 3. Comparing the images of 3D reconstruction and photos of the dissected specimens. RESULTS: 3D software could dissect and reconstruct the bones, vessels, skin and muscles, and the reconstructed photos could be shown, respectively or combinedly. On the other hand, the course, distribution, and anastomoses of the vessels could be viewed from different aspects and different layers, but the results were not completely correct, so they were not suitable for data acquisition. While the vessel systems could be observed clearly on the dissected specimens, so could the origin, course, distribution and the anastomoses of any vessel. The data acquisition could be conducted. CONCLUSIONS: The method of angiography with 3D reconstruction is very good and has considerable advantages for observing the 3D state of human blood vessels, and their distribution at different angles and different levels, but it cannot totally represent or replace the traditional dissected specimens.