Neuroscience
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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.
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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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KY-226 is a protein tyrosine phosphatase 1B (PTP1B) inhibitor that protects neurons from cerebral ischemic injury. KY-226 restores Akt (protein kinase B) phosphorylation and extracellular signal-regulated kinase (ERK) reduction in transient middle cerebral artery occlusion (tMCAO) damage. However, the mechanisms underlying the neuroprotective effects of KY-226 are unclear. ⋯ Further, KY-226 treatment restored phosphorylation of pAkt (T308) and its downstream target forkhead box protein O1 (FoxO1) (S256) in bEnd.3 cells. Collectively, we demonstrate that KY-226 protects BBB integrity by restoration of TJ proteins, an effect partly mediated by Akt/FoxO1 pathway activation. Thus, protection of BBB integrity likely underlies KY-226-induced neuroprotection in tMCAO mice.
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Review
From Early to Late Neurogenesis: Neural Progenitors and the Glial Niche from a Fly's Point of View.
Drosophila melanogaster is an important model organism used to study the brain development of organisms ranging from insects to mammals. The central nervous system in fruit flies is formed primarily in two waves of neurogenesis, one of which occurs in the embryo and one of which occurs during larval stages. In order to understand neurogenesis, it is important to research the behavior of progenitor cells that give rise to the neural networks which make up the adult nervous system. ⋯ Recent discoveries in progenitors and niche cells have led to new understandings of how the developing brain shapes its diverse regions. In this review, we attempt to summarize the distinct neural progenitors and glia in the Drosophila melanogaster central nervous system, from embryo to late larval stages, and make note of homologous features in mammals. We also outline the recent advances in this field in order to define the impact that glial cells have on progenitor cell niches, and we finally emphasize the importance of communication between glia and progenitor cells for proper brain formation.
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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.