Neuroscience
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Fear of falling increases conscious control of balance and postural threat warrants accurate anticipatory motor commands for keeping a safe body posture. This study examines the anticipatory (APAs) and compensatory (CPAs) postural adjustments generated in response to an external perturbation while individuals are positioned at two different altitudes (2 cm and 80 cm) from the floor level. The main result indicates that due to the perceived emotional threat, different agonist and antagonist muscles synergies (R and C-Indexes) are manifested, particularly during the anticipatory phase. ⋯ Interestingly, the APAs strategies were modified under different postural threats by controlling the agonist-antagonist muscles at different joints of lower extremity. For CPAs the reciprocal activation was less applied compared to muscles co-activation to unsure larger margin for compensatory adjustments as needed and re-establish the postural stability. The results indicate that when facing to a postural threat, the CNS modulates the anticipatory and compensatory phases of postural adjustments to minimize the risk of falling.
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Proteinase-activated receptor-1 (PAR1) antagonist plays a protective effect in brain injury. We investigated the potential function and mechanisms of PAR1 antagonist in ICH-induced brain injury. Results showed that PAR1 antagonist protected against neurobehavior deficits, brain edema and blood-brain barrier integrity in ICH mice via the JNK/ERK/p38 MAPK signaling pathway at 24 h after ICH. ⋯ Moreover, the protective effect of PAR1 antagonist on ICH-induced brain injury was blocked by FGL2 or TLR4 overexpression, and the levels of p-JNK, p-ERK and p-p38 MAPK were increased. Furthermore, PAR1 antagonist combined with TLR4 antagonist markedly alleviated brain injury after ICH at 72 h. Overall, PAR1 antagonist protected against short-term brain injury, and the effect of PAR1 antagonist on ICH-induced brain injury was mediated by FGL2 or TLR4.
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Glycogen synthase kinase-3β (GSK-3β) is a highly expressed kinase in the brain, where it has an important role in synaptic plasticity. Aberrant activity of GSK-3β leads to synaptic dysfunction which results in the development of several neuropsychiatric and neurological diseases. Notably, overexpression of constitutively active form of GSK-3β (GSK-3β[S9A]) in mice recapitulates the cognitive and structural defects characteristic for neurological and psychiatric disorders. ⋯ Next, characterization of miR-221* function in primary hippocampal cell culture transfected by miR-221* inhibitor, showed no structural changes in dendritic spine shape and density. Using electrophysiological methods, we found that downregulation of miR-221* increases excitatory synaptic transmission in hippocampal neurons, probably via postsynaptic mechanisms. Thus, our data reveal potential mechanism by which GSK-3β and miRNAs might regulate synaptic function and therefore also synaptic plasticity.
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Vestibular schwannoma (VS) is a benign, slow-growing neoplasm, which is an important cause of sensorineural hearing loss. Circular RNAs (circRNAs) have been widely reported to be dysregulated and participate in multiple biological processes of human diseases. However, roles of most circRNAs still remain explored. ⋯ Additionally, results of mechanism assays demonstrated that circ_0001665 could function as a sponge of microRNA-302a-3p (miR-302a-3p) to enhance Adam9 expression and to activate EGFR signaling pathway in VS cells. Eventually, it was indicated in rescue assays that circ_0001665 expedited proliferation and restrained apoptosis of VS cells via modulation on miR-302a-3p/Adam9. Collectively, our study identified a novel perspective for exploration into molecular mechanisms in VS.
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Glaucoma is a neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) death. Recently, many studies have reported that the N-methyl D-aspartate receptor 2B (NR2B) subunit is excitotoxic in the pathogenesis of glaucoma, but the molecular mechanism should be further explored. In our present study, we investigated the involvement of the NR2B-postsynaptic density protein-95 (PSD95) complex in RGC apoptosis in an experimental glaucoma animal model and determined whether inhibition of the NR2B-PSD95 interaction protected RGCs. ⋯ Levels of the apoptosis-related proteins Bax and cleaved caspase-3 decreased as the number of surviving RGCs increased. Together, our results suggest that the NR2B-PSD95 complex was involved in RGC death in the retinal I/R injury model. Tat-NR2B9c exerted a neuroprotective effect on RGC survival in the retinal I/R injury model by disrupting the NR2B-PSD95 interaction.