Neuroscience
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Angiogenesis after intracerebral hemorrhage (ICH) injury can effectively alleviate brain damage and improve neurological function. Hypoxia-inducible factor 2α (HIF-2α) is an important angiogenic regulator and exhibits protective effects in several neurological diseases; however, its role in ICH has not yet been reported. Hence, in the present study, we explored whether HIF-2α reduces ICH injury by promoting angiogenesis. ⋯ Likewise, the HIF-2α-mediated increase in phospho-VEGFR-2, cleaved-Notch1 and Notch1 expression was reversed via a VEGFR2-specific inhibitor. Taken together, our results indicate that HIF-2α promotes angiogenesis via the VEGF/Notch pathway to attenuate ICH injury. Moreover, our findings may contribute to the development of a novel strategy for alleviating ICH injury via HIF-2α-mediated upregulation of angiogenesis.
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Understanding how the brain decodes sensory information to give rise to behaviour remains an important problem in systems neuroscience. Across various sensory modalities (e.g. auditory, visual), the time-varying contrast of natural stimuli has been shown to carry behaviourally relevant information. However, it is unclear how such information is actually decoded by the brain to evoke perception and behaviour. ⋯ Further analysis revealed that the lower detection thresholds of midbrain neurons were not due to increased sensitivity to the stimulus. Rather, these were due to the fact that midbrain neurons displayed lower variability in their firing activities in the absence of stimulation, which is due to lower firing rates. Our results suggest that midbrain neurons play an active role towards enabling the detection of weak stimulus contrasts, which in turn leads to perception and behavioral responses.
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Alzheimer's disease (AD) is a neurodegenerative disease mainly associated with aging, oxidative stress and genetic mutations. There are two pathological proteins involved in AD; Amyloid-β peptide and microtubule-associated protein Tau (MAPT). The β- and γ-secretase enzyme cleaves the Amyloid precursor protein, which results in the formation of extracellular plaques in brain. ⋯ The P2Y receptors give 'find me' or 'eat me' signals to microglia to either migrate or phagocytose cellular debris. Further, the actin cytoskeleton helps microglia to mediate directed chemotaxis and neuronal repair during neurodegeneration. Hence, we aim to emphasize the connection between purinergic signaling and actin-driven mechanical movements of microglia for migration and inflammation in AD.
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Growth cone-mediated axonal outgrowth and accurate synaptic targeting are central to brain morphogenesis. Translocation of the growth cone necessitates mechanochemical regulation of cell-extracellular matrix interactions and the generation of propulsive traction forces onto the growth environment. However, the molecular mechanisms subserving force generation by growth cones remain poorly characterized. ⋯ Analysis of F-actin retrograde flow reveals that Fmn2 functions as a clutch molecule and mediates the coupling of the actin cytoskeleton to the growth substrate, via point contact adhesion complexes. Using traction force microscopy, we show that the Fmn2-mediated clutch function is necessary for the generation of traction stresses by neurons. Our findings suggest that Fmn2, a protein associated with neurodevelopmental and neurodegenerative disorders, is a key regulator of a molecular clutch activity and consequently motility of neuronal growth cones.