Neuroscience
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The damage of locus coeruleus (LC) noradrenergic neurons and associated with norepinephrine (NE) depletion are early events in Parkinson's disease (PD). Previous study showed that LC/NE neurodegeneration exacerbates dopaminergic neurotoxicity and motor deficits. However, whether the damage of LC/NE neurons contributes to non-motor symptoms in PD remain unclear. ⋯ DSP-4 treatment also exacerbated paraquat and maneb-induced decrease of glutathione peroxidase 4 (GPX4) and glutathione contents as well as increase of lipid peroxidation and expressions of gp91phox and p47phox, two subunits of NADPH oxidase, which are all involved in ferroptosis, in mice. Furthermore, exaggerated microglial activation and M1 polarization were observed in DSP-4 and paraquat and maneb co-treated mice compared with paraquat and maneb alone group. Altogether, our findings revealed a critical role of LC/NE neurodegeneration in mediating learning and memory dysfunction in a two pesticide-induced mouse PD model through ferroptosis and microglia-mediated neuroinflammation, proving novel insights into the pathogenesis of cognitive dysfunction in PD.
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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.
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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.