Mcneillhviid8093

Abnormal neuronal activity during epileptic seizures alters the properties of synaptic plasticity, and, consequently, leads to cognitive impairment. The molecular mechanism of these alterations in synaptic plasticity is still unclear. In the present study, using a 4-aminopyridine (4-AP) in vitro model, we demonstrated that epileptiform activity in rat hippocampal slices initially causes substantial enhancement of field excitatory postsynaptic potential amplitude. However, the potentiation of CA3-CA1 synapses was temporary and switched to long-term depression (LTD) within an hour. Previous studies showed that transient incorporation of calcium-permeable AMPA receptors (CP-AMPARs) is crucial for the consolidation of long-term potentiation (LTP). We confirmed that, in normal conditions, the blockage of CP-AMPARs prevented the consolidation of LTP induced by theta-burst stimulation (TBS). In contrast, the blockage of CP-AMPARs preserved synaptic potentiation induced by epileptiform activity. One hour after a period of epileptiform activity in the hippocampal slices, synaptic plasticity was substantially altered, and the TBS protocol was unable to produce LTP. Moreover, if CP-AMPARs were blocked, the TBS protocol induced LTD. Our results indicate that CP-AMPARs play an essential role in the molecular mechanism of the disturbances of synaptic plasticity caused by epileptiform activity.The gut-brain communication is increasingly being recognized as a profound effector on Parkinson's disease (PD). Gut microbiota changes have become the focus of attention. However, the mechanism leading to changes in the gut microbiota is not clear. In the present study, we found that knockout of Dcf1 (Dcf1-/-) caused changes in the gut microbiota in mice. Results indicated that the increased Proteobacteria (phylum-level) and decreased Prevotellaceae (family-level) in the microbiota composition of Dcf1-/- (KO) mice, which is consistent with the situation of PD patients. On species-level, Prevotellaceae_UCG-001 and Helicobacter_ganmani were significantly different between KO and WT mice, suggesting glycolipid metabolism disorders and inflammatory lesions in KO mice. read more In the behavior of Y-maze and Open field test, KO mice showed typical PD symptoms such as memory deficits, slowness of movement and anxiety. Further Nissl staining of brain tissue sections confirmed that the deletion of Dcf1 caused damage to amygdala neurons. These results provide a new mechanism for understanding gut microbiota changes, and provide a new basis for PD treatment from a new perspective of Gut-brain axis.The brain-gut hormone ghrelin and its receptor GHS-R1a, the growth hormone secretagogue receptor 1a, regulates diverse functions of central nervous system including stress response and mood. Both acute and chronic caloric restrictions (CR) were reported to increase endogenous ghrelin level meanwhile regulate anxiety-related behaviors; however, the causal relationship between CR-induced ghrelin elevation and anxiety are not fully established. Here, we introduced an acute (24 h) and a chronic (10wks) CR procedure to both GHS-R1a KO (Ghsr-/-) mice and WT (Ghsr+/+) littermates, and compared their anxiety-related behaviors. We found that acute CR induced anxiolytic and anti-despairing behaviors in Ghsr+/+ mice but not in Ghsr-/- mice. Ad-libitum refeeding abolished the effect of acute CR on anxiety-related behaviors. In contrast, chronic CR for 10wks facilitated despair-like behavior meanwhile inhibited anxiety-like behavior in Ghsr+/+ mice. GHS-R1a deficiency rescued despair-like behavior while did not affect anxiolytic response induced by chronic CR. In addition, we found elevated interleukin-6 (IL-6) in serum of Ghsr+/+ mice after chronic CR, but not in Ghsr-/- mice. Altogether, our findings indicated that acute CR and chronic CR have different impacts on anxiety-related behaviors, and the former is dependent on ghrelin/GHS-R1a signaling while the latter may not always be. In addition, our findings suggested that GHS-R1a-dependent elevation in serum IL-6 might contribute to increased despair-like behavior in chronic CR state.Immunoglobulin A nephropathy (IgAN) constitutes the most common primary glomerulonephritis worldwide; however, the exact pathogenesis of IgAN is unknown. Previous genome-wide analysis of microRNA (miRNA) expression in the kidney has confirmed that miRNAs are closely related to the pathological changes of IgAN. Accordingly, in this study we found that miR-27a-3p is upregulated in IgAN kidney tissues in addition to human podocytes and tubule epithelial HK2 but not mesangial cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), flow cytometry, real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays were used to verify the regulatory effects of miR-27a-3p and its inhibition on cell proliferation, apoptosis, and release of inflammatory factors in podocytes and HK2 cells. The target genes of miR-27a-3p were predicted using bioinformatics software; the identity of FosB as a target gene of miR-27a-3p was confirmed by luciferase report assay and western blot. Overall, our findings demonstrated that miR-27a-3p regulates cell apoptosis, cell proliferation, and the release of inflammatory cytokines of human podocytes and HK2 cells by directly targeting FosB. Our results therefore suggested that miR-27a-3p might be associated with the pathophysiology of IgAN and may represent a potential target for further studies related to IgAN mechanism or therapeutics.In neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, neuroinflammation induced by the microglial activation plays a crucial role. In effort to develop effective anti-neuroinflammatory compounds, different new linear polyoxygenated diarylheptanoids were synthesized. In LPS-triggered BV-2 microglial cells their ability to reduce the concentration of IL-6 and TNF-α pro-inflammatory cytokines was evaluated. Moreover, their effect on NF-κB and ATP citrate lyase (ACLY), a recently emerged target of metabolic reprogramming in inflammation, was assessed. Finally, we turned our attention to inflammatory mediators derived from the cleavage of citrate catalyzed by ACLY prostaglandin E2, nitric oxide and reactive oxygen species. All compounds showed null or minimal cytotoxicity; most of them had a great anti-neuroinflammatory activity. Diarylheptanoids 6b and 6c, bearing a halide atom and benzyl ether protective groups, exhibited the best effect since they blocked the secretion of all inflammatory mediators analyzed and reduced NF-κB and ACLY protein levels.