Neuroscience
-
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.
-
Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In this study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissue and microglia samples from mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluate its role in SAE. Analysis of mouse brain RNA-Seq revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 of repopulation and dramatically altered B2m RNA editing. ⋯ The hippocampus from sepsis mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Furthermore, the expression of complement-related genes, such as C4b and Cd47, was substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis and provides new insights into its potential role in SAE.
-
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.
-
Hyperphagia and subsequent obesity are important public health issues due to the associated risks of developing serious diseases. Certain stressors play a major role in the development of hyperphagia. In previous studies, we established a line of human growth hormone transgenic (TG) rats that exhibit hyperphagia and obesity from a young age. ⋯ These treatments did not affect the food intake of WT rats. Rearing TG rats under group housing prevented hyperphagia and hypercorticosteronemia. These results suggest that glucocorticoids are appetite stimulants, and that TG rats exhibit increased sensitivity to the appetite-stimulating effect of glucocorticoids.
-
The electrical activity of the brain, characterized by its frequency components, reflects a complex interplay between periodic (oscillatory) and aperiodic components. These components are associated with various neurophysiological processes, such as the excitation-inhibition balance (aperiodic activity) or interregional communication (oscillatory activity). However, we do not fully understand whether these components are truly independent or if different neuromodulators affect them in different ways. ⋯ By parameterizing the power spectrum into these two components, our findings reveal a robust modulation of oscillatory activity by the D2 receptor across the brain. Surprisingly, aperiodic activity was not significantly affected and exhibited inconsistent changes across the brain. This suggests a nuanced interplay between neuromodulation and the distinct components of brain oscillations, providing insights into the selective regulation of oscillatory dynamics in awake states.