Neuroscience
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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.
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Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence. Thus, we tested if PC2 null mice exhibit altered morphine-induced antinociception, tolerance and dependence. PC2 null mice and their wild-type controls were tested for baseline hot plate latency, injected with morphine (1.25-10mg/kg) and tested for antinociception 30min later. ⋯ Likewise, naloxone specific binding was increased in the brains of these mice compared to their wild-type controls. The results suggest that the PC2-derived peptides may play a functional role in morphine-induced antinociception, tolerance and dependence. Alternatively, lack of opioid peptides led to up-regulation of the MOP and altered morphine-induced antinociception, tolerance and dependence.
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Developmental exposure to arylhydrocarbon receptor (AhR) ligands abolishes sex differences in a wide range of neural structures and functions. A well-studied example is the anteroventral periventricular nucleus (AVPV), a structure that controls sex-specific luteinizing hormone (LH) release. In the male, testosterone (T) secreted by the developing testes defeminizes LH release mechanisms; conversely, perinatal AhR activation by 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) blocks defeminization. ⋯ CUG triplet repeat, RNA binding protein 2 (cugbp2) is particularly interesting because it is sex-specific, oppositely regulated by estradiol (E2) and TCDD. Moreover, it regulates the post-transcriptional processing of molecules previously linked to sexual differentiation of the brain. These findings provide new insights into how TCDD may interfere with defeminization of LH release patterns.