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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Hydrocephalus is especially prevalent in countries with limited resources, where its treatment is still a challenge. However, long-term neuropathological changes in untreated hydrocephalus remain largely unexplored. The present study looks at cortical parenchyma and neuroinflammation in acquired, chronic hydrocephalus. ⋯ IL-1β expression also peaked at 4weeks and was then down-regulated. Overall the findings indicate that neuroinflammatory features build up in the first month after hydrocephalus induction implicating marked IL-1β upregulation. The data also show that astrocytes are the main source of IL-1β in this disorder.
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Agrin is a multi-domain protein best known for its essential function during formation of the neuromuscular junction. Alternative mRNA splicing at sites named y and z in the C-terminal part of agrin regulates its interaction with a receptor complex consisting of the agrin-binding low-density lipoprotein receptor-related protein 4 (Lrp4) and the muscle-specific kinase (MuSK). Isoforms with inserts at both splice sites bind to Lrp4, activate MuSK and are synaptogenic at the neuromuscular junction. ⋯ This effect was independent of splice site z. The reduction of the gephyrin puncta density was independent of the entire extracellular part of TM-agrin but required a highly conserved serine residue in the intracellular domain of TM-agrin. These results provide further evidence for a function of TM-agrin during CNS synaptogenesis and demonstrate that different domains and alternative splicing of TM-agrin differentially affect excitatory and inhibitory synapse formation in cultured embryonic CNS neurons.