Neuroscience
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While the majority of the population is ever exposed to a traumatic event during their lifetime, only a fraction develops posttraumatic stress disorder (PTSD). Disrupted trauma memory processing has been proposed as a core factor underlying PTSD symptomatology. We used transgenic Targeted-Recombination-in-Active-Populations (TRAP) mice to investigate potential alterations in trauma-related hippocampal memory engrams associated with the development of PTSD-like symptomatology. ⋯ While no differences in the size of the hippocampal neuronal ensemble activated during fear learning were observed between groups, susceptible mice displayed a smaller ensemble activated upon remote fear memory recall in the ventral CA1, higher regional hippocampal parvalbuminneuronal density and a relatively lower activity of parvalbumininterneurons upon recall. Investigation of potential epigenetic regulators of the engram revealed rather generic (rather than engram-specific) differences between groups, with susceptible mice displaying lower hippocampal histone deacetylase 2 expression, and higher methylation and hydroxymethylation levels. These finding implicate variation in epigenetic regulation within the hippocampus, as well as reduced regional hippocampal activity during remote fear memory recall in interindividual differences in susceptibility to traumatic stress.
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Glioma is one of the most common and difficult to cure malignant primary tumors of the central nervous system. Long non-coding RNA (lncRNA) has been reported to play important functions in biological processes of many tumors, including glioma. In our study, we aimed to reveal the role and molecular mechanisms of lncRNA COX10-AS1 in regulating the progression of glioma. ⋯ In addition, we uncovered that there existed a regulatory relationship that COX10-AS1 upregulated OCR6 by sponging miR-1-3p in GBM cells, and the following rescue assays demonstrated that both miR-1-3p downregulation and origin recognition complex subunit 6 (ORC6) overexpression rescued cell viability, migration and invasion in the COX10-AS1-deficient GBM cells. Consistently, we also verified that COX10-AS1 promoted tumorigenesis of the GBM cells in vivo through modulating the miR-1-3p/ORC6 axis. On the whole, our findings indicated a novel ceRNA pattern in which COX10-AS1 elevated OCR6 expression via sponging miR-1-3p, therefore boosting tumorigenesis in glioma, and we firstly discussed the underlying mechanisms by which the COX10-AS1/miR-1-3p/ORC6 axis affected the progression of glioma.
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Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia-reperfusion injury. 4'-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia-reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. ⋯ Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia-reperfusion injury.
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Secretory clusterin (sCLU) plays an important role in the research progress of nervous system diseases. However, the physiological function of sCLU in Parkinson's disease (PD) are unclear. The purpose of this study was to examine the effects of sCLU-mediated autophagy on cell survival and apoptosis inhibition in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. ⋯ These effects were also abrogated by sCLU intervention. Activation of PI3K/AKT/mTOR signaling with MPTP inhibited autophagy in the SN of MPTP mice; however, sCLU treatment activated autophagy in MPTP-induced PD mice by inhibiting PI3K/AKT/mTOR signaling. These data indicated that sCLU treatment had a neuroprotective effect in an MPTP-induced model of PD.
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The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. ⋯ The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology.