Neuroscience
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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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Limb immobilization is known to cause significant decreases in muscle strength and muscle mass as early as two days following the onset of immobilization. However, the decline in strength surpasses the decline in muscle mass, suggesting that factors in addition to muscle loss, such as neuroplasticity, contribute to the decrease in force production. However, little is known regarding immobilization-induced neural changes, although sensorimotor regions seem to be the most affected. ⋯ The results showed changes predominantly involving cerebellar connectivity. For example, the immobilization period caused a decrease in connectivity between the motor cerebellar region of the immobilized arm and the left temporal lobe, and an increase between the same cerebellar region and the supplementary motor area. Overall, changes in connectivity occurred in regions typically associated with error detection and motor learning, suggesting a potential functional reorganization of the brain within 14 days of elbow immobilization.
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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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Anesthesia/surgery have been identified as potential factors contributing to perioperative neurocognitive disorders, with a notably heightened risk observed in aging populations. One of the primary drivers of this impairment is believed to be neuroinflammation, specifically inflammation of hippocampal microglia. Dietary restriction has demonstrated a favorable impact on cognitive impairment across various disorders, primarily by quelling neuroinflammation. ⋯ We conducted 16S rRNA sequencing to investigate the impact of dietary restriction on the intestinal flora of aged mice following anesthesia/surgery. Our findings indicate that dietary restrictions have the potential to ameliorate anesthesia/surgery-induced cognitive dysfunction. This effect is achieved through the modulation of gut microbiota, suppression of inflammatory responses in hippocampal microglia, and facilitation of neuronal repair and regeneration.
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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.