Neuroscience
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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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The cochlear nucleus, located in the brainstem, receives its afferent auditory input exclusively from the auditory nerve fibers of the ipsilateral cochlea. Noise-induced neurodegenerative changes occurring in the auditory nerve stimulate a cascade of neuroplastic changes in the cochlear nucleus resulting in major changes in synaptic structure and function. To identify some of the key molecular mechanisms mediating this synaptic reorganization, we unilaterally exposed rats to a high-intensity noise that caused significant hearing loss and then measured the resulting changes in a synaptic plasticity gene array targeting neurogenesis and synaptic reorganization. ⋯ Significant gene expression changes occurred more frequently in the VCN than the DCN and more changes were seen at 28 d versus 2 d post-exposure. We confirmed the PCR findings by in situ hybridization for Brain-derived neurotrophic factor (Bdnf), Homer-1, as well as the glutamate NMDA receptor Grin1, all involved in neurogenesis and plasticity. These results suggest that Bdnf, Homer-1 and Grin1 play important roles in synaptic remodeling and homeostasis in the cochlear nucleus following severe noise-induced afferent degeneration.
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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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Noisy galvanic vestibular stimulation (nGVS) has been shown to improve vestibular perception in healthy subjects. However, it is unclear whether both the semicircular canals (SCCs) and otolith organs contribute to this enhancement or is it confined to one of these structures. To elucidate this matter, nGVS amplitudes with optimal effect on postural control were determined in 12 healthy subjects during upright stance. ⋯ In addition, elevated baseline thresholds during the inter-aural translation task significantly correlated with a larger magnitude of improvement (R = 0.72, p = 0.01). In conclusion, nGVS appears to primarily impact otolith-mediated perception while only mildly affecting the SCCs. Thus, this stimulation approach could be a complementary candidate to vestibular implants that are currently limited to SCC-mediated vestibular function.
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The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that modify extracellular matrix components and play crucial roles in development and numerous diseases. ADAMTS18 is a member of the ADAMTS family, and genome-wide association studies made an initial association of ADAMTS18 with white matter integrity in healthy people of 72-74 years old. However, the potential roles of ADAMTS18 in central nervous system remain unclear. ⋯ Behavioral tests showed that Adamts18 KO mice had reduced levels of depression-like behaviors compared to their wild-type (WT) littermates. The increased neurite formation could be attributed in part to reduced phosphorylation levels of the collapsin response mediator protein-2 (CRMP2) due to activation of the laminin/PI3K/AKT/GSK-3β signaling pathway. Our findings revealed a critical role of ADAMTS18 in neuronal morphogenesis and emotional control in mice.