Diets rich in SFA have been implicated in Alzheimer's disease (AD). There is strong evidence to suggest that microglial activation augments the progression of AD. However, it remains uncertain whether SFA can initiate microglial activation and whether this response can cause neuronal death. Using the BV-2 microglial cell line and primary microglial culture, we showed that palmitic acid (PA) and stearic acid (SA) could activate microglia, as assessed by reactive morphological changes and significantly increased secretion of pro-inflammatory cytokines, NO and reactive oxygen species, which trigger primary neuronal death. In addition, the mRNA level of these pro-inflammatory mediators determined by RT-PCR was also increased by PA and SA. We further investigated the intracellular signalling mechanism underlying the release of pro-inflammatory mediators from PA-activated microglial cells. The present results showed that PA activated the phosphorylation and nuclear translocation of the p65 subunit of NF-kB. Furthermore, pyrrolidine dithiocarbamate, a NF-kB inhibitor, attenuated the production of pro-inflammatory mediators except for IL-6 in PA-stimulated microglia. Administration of anti-Toll-like receptor (TLR)4-neutralising antibody repressed PA-induced NF-kB activation and pro-inflammatory mediator production. In conclusion, the present in vitro study demonstrates that SFA could activate microglia and stimulate the TLR4/NF-kB pathway to trigger the production of pro-inflammatory mediators, which may contribute to neuronal death.

BackgroundOveractivated microglia is involved in various kinds of neurodegenerative diseases. Suppression of microglial overactivation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory effects of oxytocin (OT), which is a highly conserved nonapeptide with hormone and neurotransmitter properties, were investigated in vitro and in vivo.MethodsBV-2 cells and primary microglia were pre-treated with OT (0.1, 1, and 10 μM) for 2 h followed by LPS treatment (500 ng/ml); microglial activation and pro-inflammatory mediators were measured by Western blot, RT-PCR, and immunofluorescence. The MAPK and NF-κB pathway proteins were assessed by Western blot. The intracellular calcium concentration ([Ca2+]i) was determined using Fluo2-/AM assay. Intranasal application of OT was pre-treated in BALB/C mice (adult male) followed by injected intraperitoneally with LPS (5 mg/kg). The effect of OT on LPS-induced microglial activation and pro-inflammatory mediators was measured by Western blot, RT-PCR, and immunofluorescence in vivo.ResultsUsing the BV-2 microglial cell line and primary microglia, we found that OT pre-treatment significantly inhibited LPS-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, OT inhibited phosphorylation of ERK and p38 but not JNK MAPK in LPS-induced microglia. OT remarkably reduced the elevation of [Ca2+]i in LPS-stimulated BV-2 cells. Furthermore, a systemic LPS-treated acute inflammation murine brain model was used to study the suppressive effects of OT against neuroinflammation in vivo. We found that pre-treatment with OT showed marked attenuation of microglial activation and pro-inflammatory factor levels.ConclusionsTaken together, the present study demonstrated that OT possesses anti-neuroinflammatory activity and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

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COVID-19, the most severe public health problem to occur in the past 10 years, has greatly impacted people's mental health. Colleges in China have reopened, and how to prevent college students from suffering secondary damage due to school reopening remains elusive. This cross-sectional study was aimed to evaluate the psychological impact of COVID-19 after school reopening and explore via machine learning the factors that influence anxiety and depression among students. Among the 478 valid online questionnaires collected between September 14th and September 20th, 74 (15.5%) showed symptoms of anxiety (by the Self-Rating Anxiety Scale), and 155 (32.4%) showed symptoms of depression (by Patient Health Questionnaire-9). Descriptive analysis of basic personal characteristics indicated that students at a higher grade, having relatives or friends who have been infected, fearing being infected, and having a pessimistic attitude to COVID-19 easily experience anxiety or depression. The Synthetic Minority Oversampling Technique (SMOTE) was utilized to counteract the imbalance of retrieved data. The Akaike Information Criterion (AIC) and multivariate logistic regression were performed to explore significant influence factors. The results indicate that exercise frequency, alcohol use, school reopening, having relatives or friends who have been infected, self-quarantine, quarantine of classmates, taking temperature routinely, wearing masks routinely, sleep quality, retaining holiday, availability of package delivery, take-out availability, lockdown restriction, several areas in school closed due to COVID-19, living conditions in the school, taking the final examinations after school reopening, and the degree to which family economic status is influenced by COVID-19 are the primary influence factors for anxiety or depression. To evaluate the effect of our model, we used 5-fold cross-validation, and the average area under the curve (AUC) values of the receiver operating characteristic (ROC) curves of anxiety and depression on the test set reached 0.885 and 0.806, respectively. To conclude, we examined the presence of anxiety and depression symptoms among Chinese college students after school reopening and explored many factors influencing students' mental health, providing reasonable school management suggestions.

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Thiamine (Vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation and neurodegeneration, which are commonly observed in neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Thiamine metabolites may serve as promising biomarkers for neurodegenerative diseases and thiamine supplementations exhibit therapeutic potential for patients of some neurodegenerative diseases. Experimental TD has been used to model aging-related neurodegenerative diseases. However, to date, the cellular and molecular mechanisms underlying TD-induced neurodegeneration are not clear. Recent research evidence indicates that TD causes oxidative stress, endoplasmic reticulum (ER) stress and autophagy in the brain, which are known to contribute to the pathogenesis of various neurodegenerative diseases. In this review, we discuss the role of oxidative stress, ER stress and autophagy in TD-mediated neurodegeneration. We propose that it is the interplay of oxidative stress, ER stress and autophagy that contributes to TD-mediated neurodegeneration.

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