Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus.

Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant and in the gut, but less abundant and . Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum.

The secretome of microglia induced by IL-4 of IFN-γ differently regulate proliferation, differentiation and survival of adult neural stem/progenitor cell by targeting the PI3K-Akt pathway.

Microglia has been reported to be able to regulate the proliferation, differentiation and survival of adult neural stem/progenitor cells (NSPCs) by modulating the microenvironment, which results in different consequences of adult neurogenesis. However, whether the microglial activation is beneficial or harmful to NSPCs is still controversial because of the complexity and variability of microglial activation phenotypes. In this study, we systematically explored the activation phenotypes of IFN-γ- or IL-4-induced microglia at different time after stimulation, and investigated the effects of the secretome of different phenotype of microglia on the process of proliferation, differentiation and survival of NSPCs.

Asperosaponin VI ameliorates the CMS-induced depressive-like behaviors by inducing a neuroprotective microglial phenotype in hippocampus via PPAR-γ pathway.

Background: The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here, we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.

Methods: Mice were exposed to CMS for 3 weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another 3 weeks.

Mapping the Plasticity of Morphology, Molecular Properties and Function in Mouse Primary Microglia.

Microglia exert diverse functions by responding in diverse ways to different stimuli, yet little is known about the plasticity of various phenotypes that microglia display. We used interferon (IFN)-γ, interleukin (IL)-4 and IL-10 to induce different phenotypes in mouse primary microglia. RNA sequencing was used to identify genes differentially expressed in response to stimulation, and the different stimulated populations were compared in terms of morphology, proliferative capacity, phagocytic ability and neurotoxicity.

Asperosaponin VI inhibits LPS-induced inflammatory response by activating PPAR-γ pathway in primary microglia.

Microglia cells are the main mediators of neuroinflammation. Activation of microglia often aggravates the pathological process of various neurological diseases. Natural chemicals have unique advantages in inhibiting microglia-mediated neuroinflammation and improving neuronal function.

Mouse Astrocytes Promote Microglial Ramification by Releasing TGF-β and Forming Glial Fibers.

The morphology of microglial cells is often closely related to their functions. The mechanisms that regulate microglial ramification are not well understood. Here we reveal the biological mechanisms by which astrocytes regulate microglial ramification.

Priming of microglia with IFN-γ impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects.

Neuroinflammation driven by interferon-gamma (IFN-γ) and microglial activation has been linked to neurological disease. However, the effects of IFN-γ-activated microglia on hippocampal neurogenesis and behavior are unclear. In the present study, IFN-γ was administered to mice via intracerebroventricular injection.

IL-4 and IL-10 promotes phagocytic activity of microglia by up-regulation of TREM2.

Triggering receptor expressed on myeloid cells-2 (TREM2) is an innate immune receptor that promotes phagocytosis by microglia. However, whether TREM2 is related to the stimulus-dependent phagocytic activity of microglia is unclear. In this study, the primary cultured microglia were stimulated with interferon (IFN)-γ, interleukin (IL)-4, and interleukin (IL)-10, respectively, and their phagocytic activity against microbeads and apoptotic neural stem cells (NSCs) was measured.

The antidepressant effects of asperosaponin VI are mediated by the suppression of microglial activation and reduction of TLR4/NF-κB-induced IDO expression.

Aim: Indoleamine 2,3-dioxygenase 1 (IDO) is responsible for the progression of the kynurenine pathway, which has been implicated in the pathophysiology of inflammation-induced depression. It has been reported that asperosaponin VI (ASA VI) could play a neuroprotective role through anti-inflammatory and antioxidant. In this study, we examined the antidepressant effect of ASA VI in lipopolysaccharide (LPS)-treated mice and further explored its molecular mechanism by looking into the microglial kynurenine pathway.