Neuroscience
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Language comprehension requires semantic processing of individual words and their context within a sentence. Well-characterized event-related potential (ERP) components (the N400 and late positivity component (LPC/P600)) provide neuromarkers of semantic processing, and are robustly evoked when semantic errors are introduced into sentences. These measures are useful for evaluating semantic processing in clinical populations, but it is not known whether they can be evoked in more severe neurodevelopmental disorders where explicit attention to the sentence inputs cannot be objectively assessed (i.e., when sentences are passively listened to). ⋯ Statistically distinct topographic distributions during passive versus active paradigms pointed to distinct generator configurations for semantic processing as a function of attention. Covert semantic processing continues in neurotypical adolescents when explicit attention is withdrawn from sentence inputs. As such, this approach could be used to objectively investigate semantic processing in populations with communication deficits.
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This study investigates the therapeutic effect of astrocyte-derived extracellular vesicles (EVs) in mitigating neurotoxicity-induced transcriptome changes, mitochondrial function, and base excision repair mechanisms in human brain endothelial cells (HBECs). Neurodegenerative disorders are marked by inflammatory processes impacting the blood-brain barrier (BBB) that involve its main components- HBECs and astrocytes. Astrocytes maintain homeostasis through various mechanisms, including EV release. ⋯ High-throughput RNA sequencing revealed that exposure to Na2Cr2O7 suppressed immune response genes. The addition of astrocyte-derived EVs resulted in the dysregulation of long noncoding RNAs impacting genes associated with brain development and angiogenesis. These findings reveal the positive impact of astrocytes-derived EVs in mitigating neurotoxicity and as potential therapeutic avenues for neurodegenerative diseases.
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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.
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Cortical proprioceptive processing of intermittent, passive movements can be assessed by extracting evoked and induced electroencephalographic (EEG) responses to somatosensory stimuli. Although the existent prior research on somatosensory stimulations, it remains unknown to what extent ongoing volitional muscle activation modulates the proprioceptive cortical processing of passive ankle-joint rotations. Twenty-five healthy volunteers (28.8 ± 7 yr, 14 males) underwent a total of 100 right ankle-joint passive rotations (4° dorsiflexions, 4 ± 0.25 s inter-stimulus interval, 30°/s peak angular velocity) evoked by a movement actuator during passive condition with relaxed ankle and active condition with a constant plantarflexion torque of 5 ± 2.5 Nm. ⋯ Proprioceptive stimuli during the active condition elicited robustly ∼26 % larger evoked response and ∼38 % larger beta suppression amplitudes, but ∼42 % weaker beta rebound amplitude over the primary sensorimotor cortex than the passive condition, with no differences in terms of response latencies. These findings indicate that the active volitional motor task during naturalistic proprioceptive stimulation of the ankle joint enhances related cortical activation and reduces related cortical inhibition with respect to the passive condition. Possible factors explaining these results include mechanisms occurring at several levels of the proprioceptive processing from the peripheral muscle (i.e. mechanical, muscle spindle status, etc.) to the different central (i.e. spinal, sub-cortical and cortical) levels.
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The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. ⋯ We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport.