Neuroscience
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Disrupted neuronal intracellular trafficking is often related with protein aggregates present in the brain during neurodegenerative diseases such as Alzheimer's. Impairment of intracellular transport may be related to Rab proteins, a class of small GTPases responsible for trafficking of organelles and vesicles. Deficit in trafficking between the endoplasmic reticulum (ER) and Golgi apparatus mediated by Rab1 and 6 may lead to increased unfolded protein response (UPR) and ER stress and remodeling. ⋯ Rab1 levels and cell viability decreased, whereas Rab6, UPR proteins and ER remodeling increased during protein aggregation, which were restored to normal levels after exogenous expression of Rab1. These results suggest that decrease of Rab1 levels contributes to ER stress and remodeling, while maintaining the elevated expression of Rab1 prevented impairment of cell viability during protein aggregation. In conclusion, Rab1 is a significant player to maintain intracellular homeostasis and its expression may mitigate ER dysfunction in the context of neurodegeneration-related protein inclusions.
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Extracellular vesicles are lipid bilayer-enclosed extracellular structures. Although the term extracellular vesicles is quite inclusive, it generally refers to exosomes (<200 nm), and microvesicles (~100-1000 nm). Such vesicles are resistant to degradation and can contain proteins, lipids, and nucleic acids. ⋯ The influence that such extracellular vesicles might exert on peripheral nerve regeneration is just beginning to be investigated. In the current studies we show that muscle-derived extracellular vesicles significantly influence the anatomical accuracy of motor neuron regeneration in the rat femoral nerve. These findings suggest a basic cellular mechanism by which target end-organs could guide their own reinnervation following nerve injury.
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Studies have shown that a certain dose of dexamethasone can improve the survival rate of patients with sepsis, and in sepsis associated encephalopathy (SAE), autophagy plays a regulatory role in brain function. Here, we proved for the first time that small-dose dexamethasone (SdDex) can regulate the autophagy of cerebral cortex neurons in SAE rats and plays a protective role. Cortical neurons were cultured in vitro in a septic microenvironment and a sepsis rat model was established. ⋯ Furthermore, the HdDex group exhibited the most obvious apoptosis. SdDex can regulate autophagy of cortical neurons by inhibiting the mTOR signaling pathway and plays a protective role. Brain damage induced by HdDex may be related to the activation of apoptosis.