Neuroscience
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Stress, a risk factor for major depressive disorder and Alzheimer disease, leads to the release of high-mobility group box-1 (HMGB1) protein, which in turn causes neuroinflammation. The mechanism underlying stress-induced HMGB1 release is unknown, but stress-associated glucocorticoids could be involved. Primary cultured rat cortical microglia and neurons were treated with corticosterone, a stress-associated glucocorticoid, and HMGB1 release was measured by ELISA and western blotting to test this hypothesis. ⋯ Immunocytochemistry showed that HMGB1 translocated from the nucleus to the cytoplasm following dexamethasone or dexamethasone-BSA treatment through glucocorticoid receptors. The present findings suggest that glucocorticoids stimulate microglial membrane glucocorticoid receptors and trigger cytoplasmic translocation and extracellular release of nuclear HMGB1. Thus, under stress conditions, glucocorticoids induce microglial HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders.
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Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood-brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. ⋯ The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation.
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Migraine is a complex neurological disorder with neuroinflammation playing a crucial role in its pathogenesis. This review provides an overview of the neuroinflammation mechanisms in migraine, focusing on both cellular and molecular aspects. At the cellular level, we examine the role of glial cells, including astrocytes, microglia, oligodendrocytes in the central nervous system, and Schwann cells and satellite glial cells in the peripheral nervous system. ⋯ Recent advancements, such as [11C] PBR28-targeted imaging for visualizing astrocyte activation and single-cell sequencing for exploring cellular heterogeneity, represent breakthroughs in understanding the mechanisms of neuroinflammation in migraine. By considering factors for personalized treatments, estrogen and TRPM8 emerge as promising therapeutic targets regarding sexual dimorphism. These advancements may help bridge the gap between preclinical findings and clinical applications, ultimately leading to more precise and personalized options for migraine patients.
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Auditory spatial attention detection (ASAD) aims to decipher the spatial locus of a listener's selective auditory attention from electroencephalogram (EEG) signals. However, current models may exhibit deficiencies in EEG feature extraction, leading to overfitting on small datasets or a decline in EEG discriminability. Furthermore, they often neglect topological relationships between EEG channels and, consequently, brain connectivities. ⋯ EEG electrodes over the frontal cortex are most important for ASAD tasks, followed by those over the temporal lobe. Additionally, the proposed model performs well even on small datasets. This study contributes to a deeper understanding of the neural encoding related to human hearing and attention, with potential applications in neuro-steered hearing devices.
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Alzheimer's disease (AD) remains a pressing global health concern, necessitating comprehensive investigations into its underlying molecular mechanisms. While the late-stage pathophysiology of this disease is well understood, it is crucial to examine the role of amyloid beta oligomers (Aβo), which form in the brain during the early stages of disease development. These toxic oligomers could affect neuronal viability and generate oxidative stress in the brain. ⋯ Our study also revealed the involvement of less-explored proteins like MYH9, CISD1, and SNRNP70, which play critical roles in cytoskeletal dynamics, mitochondrial function, and RNA splicing, respectively. These findings underscore the complex pathophysiology of AD, highlighting potential biomarkers and therapeutic targets for early intervention. The present study advances the understanding of Aβo-induced oxidative stress and neuronal damage, providing a foundation for future research into early-stage AD diagnosis and subsequent treatment strategies.