Neuroscience
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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.
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Ethanol is one of the most commonly used and abused substances in the world. While the behavioral effects of ethanol are well characterized, mechanisms of its action on neurons and synapses remain elusive. Prior research suggested that ethanol could affect neurons by interfering with metabolism of biologically active molecules, such as adenosine. ⋯ We conclude that A1Rs are not involved in mediating effects of ethanol on synaptic transmission in mouse visual cortex. However, A1Rs are necessary for development of mechanisms mediating facilitation at some excitatory synapses. Our results add evidence for the diversity of ethanol's effects and mechanisms of action on synaptic transmission in different brain structures, and even in the same brain area (visual cortex) in different species, rats vs mice.
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Ischaemic stroke is a major cause of morbidity and mortality worldwide. Blood clotting and thromboembolism play a central role in the pathogenesis of ischaemic stroke. An increasing number of recent studies indicate changes in blood clot structure and composition in patients with ischaemic stroke. ⋯ Mechanisms that drive clot composition and architecture such as neutrophil extracellular traps and clot contraction are also discussed. We find that, while in vitro clot structure in plasma samples from ischaemic stroke patients are consistently altered, showing denser clots that are more resistant to fibrinolysis, current data on the composition and architecture of ex vivo clots obtained by thrombectomy are more variable. With the potential of advances in technologies underpinning both the imaging and retrieving of clots, we expect that future studies in this area will generate new data that is of interest for the diagnosis, optimal treatment strategies and clinical management of patients with ischaemic stroke.
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The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. ⋯ Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy.
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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.