Neuroscience
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Kynurenine pathway metabolites (KPM) are thought to be synthesized mainly by non-neuronal cells in the mammalian brain. KPM are of particular interest because several studies demonstrated their implication in various disorders of the nervous system. Among KPM is xanthurenic acid (XA) deriving from the catabolism of 3-hydroxykynurenine. ⋯ Our results also reveal that XA-like immunoreactivity is not expressed by glial cells. To double-check our findings, we have also used another XA antibody obtained from a commercial source to confirm the neuronal expression of XA. Together, our results suggest that, differently to several other KPM produced by glial cells, XA exhibits a neuronal distribution in the mouse brain.
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SLC26A4 mutations cause fluctuating and progressive hearing loss associated with enlargement of the vestibular aqueduct (EVA). SLC26A4 encodes a transmembrane anion exchanger called pendrin expressed in nonsensory epithelial cells of the lateral wall of cochlea, vestibular organs and endolymphatic sac. We previously described a transgenic mouse model of EVA with doxycycline (dox)-inducible expression of Slc26a4 in which administration of dox from conception to embryonic day 17.5 (DE17.5) resulted in hearing fluctuation between 1 and 3months of age. ⋯ These findings suggest that stabilization of hearing by readministration of dox at P6 is mediated by pendrin expression in spindle-shaped cells. We conclude that early re-induction of Slc26a4 expression can prevent fluctuation of hearing in our Slc26a4-insufficient mouse model. Restoration of SLC26A4 expression and function could reduce or prevent fluctuation of hearing in EVA patients.
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Thrombolysis with recombinant tissue plasminogen activator (rtPA) is the most effective drug treatment for acute ischemic stroke within 4.5h after symptom onset. However, the use of rtPA may increase the risk of hemorrhagic transformation (HT), particularly when it is administered after the first 4.5h. However, no effective treatments are available to reduce the HT risk. ⋯ Additionally, rtPA administration upregulated p-Cx43 expression in hypoxia/reoxygenation (H/R)-exposed brain endothelial cells. These effects were suppressed by the phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126. We suggest that rtPA-associated hemorrhage due to an alteration in the integrity of the BBB is highly associated with an increase in p-Cx43 resulting from the activation of the PI3K and ERK pathways.
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To date, decoding accuracy of actual or imagined pointing movements to targets in 3D space from electroencephalographic (EEG) signals has remained modest. The reason may pertain to the fact that these movements activate essentially the same neural networks. In this study, we aimed at testing whether repetitive pointing movements to each of the targets promotes the development of segregated neural patterns, resulting in enhanced decoding accuracy. ⋯ A subset of electrodes, mainly over the contralateral sensorimotor areas, was found to provide most of the discriminative features for all tested conditions. Time proximity between trained and tested blocks was found to enhance decoding accuracy of target location both by target non-specific and specific mechanisms. Our findings suggest that movement repetition promotes the development of distinct neural patterns, presumably by the formation of target-specific kinesthetic memory.
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Axonal loss contributes to induction of diabetic peripheral neuropathy. Sildenafil, a phosphodiesterase type 5 inhibitor, ameliorates neurological dysfunction in diabetic peripheral neuropathy. However, the direct effect of high glucose and sildenafil on axonal growth has not been extensively investigated. ⋯ In contrast, sildenafil significantly reversed high glucose-reduced miR-146a levels and high glucose-increased IRAK1 and TRAF6. Gain- and loss-of function of miR-146a in DRG neurons revealed that miR-146a mediated the local effect of high glucose on the distal axonal growth. These in vitro data provide new insights into molecular mechanisms of diabetic peripheral neuropathy.