Neuroscience
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Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) that frequently affects the optic nerve and spinal cord. Interleukin-6 (IL-6) is considered a key cytokine in the pathogenesis of NMOSD, and the level of IL-6 is significantly increased in the sera and cerebrospinal fluid (CSF) of patients with NMOSD. We have reported that the production of IL-6 depends on the JAK/STAT3 signaling pathway. ⋯ Then, Western blotting and immunocytochemistry showed that NMO-IgG can activate the intracellular NF-κB signaling pathway. Finally, it was found that S3633, an inhibitor of the NF-κB signaling pathway, can effectively inhibit the increase in IL-6 levels. These results prove that the production of IL-6 is partly mediated by the NF-κB signaling pathway, providing a potential effective strategy for targeted treatment of NMOSD.
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The hypothalamic-pituitary-adrenal (HPA) axis mediates the physiological response to stressors and also synchronizes different physiological systems to environmental cues. Changes in day length (i.e., photoperiod) as well as chronic exposure to stressors are known to impact the HPA axis activity regulating the levels of glucocorticoid hormones. Over-exposure to inappropriate levels of glucocorticoids has been implicated in increased disease risk. ⋯ The gene expression analyses of key regulators of the HPA axis also indicated a sex-dependent effect with opposite patterns in the pituitary and adrenal glands. CVS effects on behavior were limited and related to an anxiety-like phenotype in both sexes, regardless of photoperiod condition. Our findings highlight sex-specific differences in the HPA axis and also sex-dependent effects of CVS on physiological parameters.
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Neuroinflammation is an important feature in the pathogenesis and progression of central nervous system (CNS) diseases including Alzheimer's disease (AD). One of the widely used animal models of peripherally induced neuroinflammation and neurodegeneration is a lipopolysaccharide (LPS)-induced inflammation mouse model. An acute LPS administration has been widely used for investigation of inflammation-associated disease and testing inflammation-targeting drug candidates. ⋯ Moreover, LPS treatment in mice caused significantly increased protein expression of GluN1 receptor in the brain cortex. The revealed perturbations in the LPS-induced inflammation mouse model may give insight into the mechanisms underlying inflammation-associated CNS diseases. In addition, the finding of the study provide important information about the appropriate use of the model during target validation and drug candidate testing.