Neuroscience
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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.
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Resilience to stress can be obtained by adjusting the stress-response set point during postnatal sensory development. Recent studies have implemented epigenetic mechanisms to play leading roles in improving resilience. We previously found that better resilience to heat stress in chicks can be achieved by conditioning them to moderate heat stress during their critical developmental period of thermal control establishment, 3 days posthatch. ⋯ The observed changes in DNA methylation can be explained by decreased activity of the enzyme DNA methyltransferase as a result of the PARPi injection. Furthermore, evaluation of the DNA-methylation pattern along the CRH intron showed a reduction in 5mC% as a result of PARPi treatment, alongside a reduction in CRH mRNA expression. Thus, PARPi treatment can affect DNA methylation, which can alter hypothalamic-pituitary-adrenal (HPA) axis anchors such as CRH, thereby potentially enhancing long-term resilience to heat stress.