A Dysregulated Endocannabinoid-Eicosanoid Network Supports Pathogenesis in a Mouse Model of Alzheimer's Disease

SummaryAlthough inflammation in the brain is meant as a defense mechanism against neurotoxic stimuli, increasing evidence suggests that uncontrolled, chronic, and persistent inflammation contributes to neurodegeneration. Most neurodegenerative diseases have now been associated with chronic inflammation, including Alzheimer's disease (AD). Whether anti-inflammatory approaches can be used to treat AD, however, is a major unanswered question. We recently demonstrated that monoacylglycerol lipase (MAGL) hydrolyzes endocannabinoids to generate the primary arachidonic acid pool for neuroinflammatory prostaglandins. In this study, we show that genetic inactivation of MAGL attenuates neuroinflammation and lowers amyloid β levels and plaques in an AD mouse model. We also find that pharmacological blockade of MAGL recapitulates the cytokine-lowering effects through reduced prostaglandin production, rather than enhanced endocannabinoid signaling. Our findings thus reveal a role of MAGL in modulating neuroinflammation and amyloidosis in AD etiology and put forth MAGL inhibitors as a potential next-generation strategy for combating AD

Correlation Analysis of Mineral Element Content and Sensory Quality of National Geographical Sign Product--Olecranon Peaches in Lianping

Microwave digestion-inductively coupled plasma astigmatism (ICP-AES) was used to analyze the contents of mineral elements (including K, P, Mg, Ca, Na, Fe, Cu, Mn, B, Zn, Se, Li) in 54 Olecranon Peaches collected from Shangping town, Lianping County. The obtained data was analyzed by Correlation analysis (CA), combined with fruit reducing sugar (RS%), sugar-acid ratio (S/A) and sensory scores. The results showed that in the tested samples, it had a significant positive correlation between S/A sugar-acid ratio and sensory evaluation. S/A was negatively correlated with P contents. The P contents were positively correlated with the K, Mg contents. The Mg contents were positively correlated with the K, Na contents. The Na contents were positively correlated with the Mn contents. The contents of Mn were positively correlated with RS% ratios of reducing sugar

Legislative Documents

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Additional file 3: of Inhibition of 2-AG hydrolysis differentially regulates blood brain barrier permeability after injury

Figure S1. In vivo selectivity of CPD-4645. Levels of inhibition of MAGL, ABHD6, and FAAH in the brain after 10 mg/kg subcutaneous dose of CPD-4645 at given tie point as determined by activity-based protein profiling using the pan-serine hydrolase probe FP-rhodamine. Full MAGL inhibition was normalized by effect seen at 2 h post-subcutaneous administration of 16 mg/kg JZL-184. (TIFF 1521 kb

Additional file 1: of Inhibition of 2-AG hydrolysis differentially regulates blood brain barrier permeability after injury

Table S1. Differentially regulated genes. Differentially regulated genes (increased or decreased by at least twofold) and p values for LPS-vehicle vs sham-vehicle and LPS-CPD-4645 vs LPS-vehicle groups. (XLSX 294 kb