Neuroscience
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Hydrogen peroxide (H2O2) is one of the reactive oxygen species (ROS), endogenously produced during metabolism, which acts as a second messenger. In skeletal muscles, hypoxia- or hyperthermia-induced increase in H2O2 might affect synaptic transmission by targeting the most redox-sensitive presynaptic compartment (Giniatullin et al., 2006). However, the effects of H2O2 as a signal molecule have not previously been studied in different patterns of the synaptic activity. ⋯ We found that: (i) H2O2 at low micromole concentrations inhibited both spontaneous and evoked transmitter releases from the motor nerve terminals in a use-dependent manner, (ii) the antioxidant N-acetylcysteine (NAC) eliminated these depressant effects, (iii) the influence of H2O2 was not associated with lipid oxidation suggesting a pure signaling action, (iv) the intracellular oxidant Chloramine-T or (v) the glutathione depletion produced similar to H2O2 depressant effects. Taken together, our data revealed the effective inhibition of neurotransmitter release by ROS, which was proportional to the intensity of synaptic activity at the neuromuscular junction. The combination of various oxidants suggested an intracellular location for redox-sensitive sites responsible for modulation of the synaptic transmission in the skeletal muscle.
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Processes associated with human brain development and function are exceedingly complex, limiting our capacity to investigate disease status and potential treatment strategies in vitro. Recent advancements in human cerebral organoid systems-which replicate early stage neural tube formation, neuroepithelium differentiation, and whole-brain regional differentiation-have allowed researchers to generate more accurate models of brain development and disease. ⋯ In this review, we provide an overview of various neural differentiation technologies, as well as a critical analysis of their strengths and limitations. We primarily focus on the generation of three-dimensional brain organoid systems and their application in infectious disease modeling, high-throughput compound screening, and neurodevelopmental disease modeling.
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Despite extensive literature showing damages in the sensorimotor projection fibers of children with hemiplegic cerebral palsy (HCP), little is known about how these damages affect the global brain network. In this study, we assess the relationship between the structural integrity of sensorimotor projection fibers and the integrity of intergyral association white matter connections in children with HCP. Diffusion tensor imaging was performed in 10 children with HCP and 16 typically developing children. ⋯ Using the whole-brain parcellation method, we tracked the short-, middle-, and long-range association fibers. We observed for the more affected hemisphere of children with HCP: (i) an increase in axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) for the STh and ThC fibers; (ii) a decrease in fractional anisotropy (FA) and an increase in MD and RD for the CST and SMU fibers; in (iii) a decrease in FA and an increase in AD, MD, and RD for the middle- and long-range association fibers; and (iv) an association between the integrity of sensorimotor projection and intergyral association fibers. Our findings indicate that altered structural integrity of the sensorimotor projection fibers disorganizes the intergyral association white matter connections among local and distant regions in children with HCP.
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Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. ⋯ The overall results showed myxobacterial extracts, especially from the strains Archangium sp. UTMC 4070 and Cystobacter sp. UTMC 4073, were able to protect human primary astrocytes from oxidative stress.
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MicroRNAs have been reported to be an important pathophysiological factor in neuropathic pain. However, the potential mechanism through which miRNAs function in neuropathic pain remains unclear. The purpose of this study was to explore the potential role of mir-34c in neuropathic pain in a mouse model of chronic constriction injury (CCI). ⋯ We also demonstrated that miR-34c suppressed the expression of NLRP3 by directly binding the 3'-untranslated region. Overexpression of miR-34c decreased the protein levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the spinal cord in CCI mice. Together, our results indicated that miR-34c may inhibit neuropathic pain development in CCI mice through inhibiting NLRP3-mediated neuroinflammation.