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. Mice received intraperitoneal injection of ruxolitinib to inhibit the JAK/STAT1 pathway or injection of minocycline to inhibit microglial activation. During a 7-day period, mice were assessed for depressive-like behaviors and cognitive impairment based on a series of behavioral analyses. Effects of the activated microglia on neural stem/ precursor cells (NSPCs) were examined, as was pro-inflammatory cytokine expression by activated microglia. We showed that IFN-γ-injected animals showed long-term adult hippocampal neurogenesis reduction, behavior despair, anhedonia, and cognitive impairment. Chronic activation with IFN-γ induces reactive phenotypes in microglia associated with morphological changes, population expansion, MHC II and CD68 up-regulation, and pro-inflammatory cytokine (IL-1β, TNF-α, IL-6) and nitric oxide (NO) release. Microglia isolated from the hippocampus of IFN-γ-injected mice suppressed NSPCs proliferation and stimulated apoptosis of immature neurons. Inhibiting of the JAK/STAT1 pathway in IFN-γ-injected animals to block microglial activation suppressed microglia-mediated neuroinflammation and neurogenic injury, and alleviated depressive-like behaviors and cognitive impairment. Collectively, these findings suggested that priming of microglia with IFN-γ impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects. Targeting microglia by modulating levels of IFN-γ the brain may be a therapeutic strategy for neurodegenerative diseases and psychiatric disorders.

Aim: Indoleamine 2, 3-dioxygenase (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 LPS-treated mice and further explored its molecular mechanism by insight into the microglial kynurenine pathway.Methods: To produce the model, lipopolysaccharide (LPS) (0.83 mg/kg) was administered intraperitoneally to mice. The mice received ASA Ⅵ (10 mg/kg, 20mg/kg, 40mg/kg and 80mg/kg, i.p.) thirty minutes prior to LPS injection. Depressive-like behaviors were evaluated based on the duration of immobility in the forced swim test. Microglial activation and . CC-BY-NC-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted March 15, 2020. ;

Background The ternary cropping system of Gastradia elata depends on a symbiotic relationship with the mycorrhizal fungi Armillaria mellea, which decays wood to assimilate nutrition for the growth of G. elata. The composition of microbe flora as key determinants of rhizoshere and mycorrhizoshere soil fertility and health was investigated to understand how G. elata and A. mellea impacted on its composition. The next generation pyrosequencing analysis was applied to assess the shift of structure of microbial community in rhizoshere of G. elata and mycorrhizoshere of A. mellea compared to the control sample under agriculture process. Results The root-associated microbe floras were significantly impacted by rhizocompartments (including rhizoshere and mycorrhizoshere) and agriculture process. Cropping process of G. elata enhanced the richness and diversity of the microbial community in rhizoshere and mycorrhizoshere soil. Furthermore, planting process of G. elata significantly reduced the abundance of phyla Basidiomycota, Firmicutes and Actinobacteria, while increased the abundance of phyla Ascomycota, Chloroflexi, Proteobacteria, Planctomycetes, and Gemmatimonadetes in rhizoshere and mycorrhizoshere. Besides, A. mellea and G. elata significantly enriched several members of saprophytoic and pathogenic fungus (i.e., Exophiala, Leptodontidium, Cosmospora, Cercophora, Metarhizium, Ilyonectria, and Sporothrix), which will enhance the possibility of G. elata disease incidence. At the same time, the ternary cropping system significantly deterred several members of beneficial ectomycorrhizal fungus (i.e., Russula, Sebacina, and Amanita), which will reduce the ability to protect G. elata from diseases. Conclusions In the ternary cropping system of G. elata, A. mellea and G. elata lead to imbalance of microbial community in rhizoshere and mycorrhizoshere soil, suggested that further studies on maintaining the balance of microbial community in A. mellea mycorrhizosphere and G. elata rhizosphere soil under field conditions may provide a promising avenue for high yield and high quality G. elata.