Neuroscience
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Anodal transcranial direct current stimulation (tDCS) is known to increase the force-generating capacity of the skeletal muscles. However, when tDCS is concurrently combined with a motor task, interference may occur that hinders tDCS effects. Here, we tested the interaction and time course of tDCS effects on force production when paired with a low-level force-matching task. ⋯ There was no significant effect for knee flexion. This suggests that interference does not occur for force production tasks when tDCS is combined with a motor task. Rather, the task appears to aid and isolate the effects to the muscle groups involved in the task.
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htau mice are deficient of murine tau but express all six human tau isoforms, leading to gradual tau misprocessing and aggregation in brain areas relevant to Alzheimer's disease. While histopathological changes in htau mice have been researched in the past, we focused here on functional consequences of human tau accumulation. htau mice and their background controls - murine tau knock-out (mtau(-/-)) and C57Bl/6J mice - underwent a comprehensive trial battery to investigate species-specific behavior, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory as well as acquisition, retention and extinction of contextual fear at two, four, six, nine and twelve months of age. In htau mice, tau pathology was already present at two months of age, whereas deficits in food burrowing and spatial working memory were first noted at four months of age. ⋯ Aging mtau(-/-) mice also exhibited increased body mass and locomotor activity. These data highlight that reduced food-burrowing performance was the most robust aspect of the htau phenotype with aging. htau and mtau(-/-) deficits in food burrowing pointed at the necessity of intact tau systems for daily life activities. While some htau and mtau(-/-) deficits overlap, age differences between the two genotypes may reflect distinct functional effects and compared to C57Bl/6J mice, the htau phenotype appeared stronger than the mtau(-/-) phenotype at young ages but milder with aging.
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Activation of angiotensinergic pathways by central aldosterone (Aldo)-mineralocorticoid receptor (MR) pathway plays a critical role in angiotensin II (Ang II)-induced hypertension. The subfornical organ (SFO) contains both MR and angiotensin II type 1 receptors (AT1R) and can relay the signals of circulating Ang II to downstream nuclei such as the paraventricular nucleus (PVN), supraoptic nucleus (SON) and rostral ventrolateral medulla (RVLM). In Wistar rats, subcutaneous (sc) infusion of Ang II at 500ng/min/kg for 1 or 2weeks increased reactive oxygen species (ROS) as measured by dihydroethidium (DHE) staining in a nucleus - specific pattern. ⋯ Both MR- and AT1aR-siRNA in the SFO prevented most of the Ang II-induced hypertension as assessed by telemetry. These results indicate that Aldo-MR signaling in the SFO is needed for the activation of Ang II-AT1R-ROS signaling from the SFO to the PVN and RVLM. Activation of Aldo-MR signaling from the SFO to the SON may enhance AT1R dependent activation of pre-sympathetic neurons in the PVN.
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The intergeniculate leaflet (IGL) is a flat retinorecipient thalamic structure implicated in orchestrating circadian rhythm, historically considered to be a subdivision of the neighboring ventrolateral geniculate nucleus (VLG). IGL consists of two main neuronal subpopulations: enkephalinergic and neuropeptide Y (NPY)-synthesizing cells. These cell types have different functions, connectivity and firing pattern in vivo, which suggest that they have different membrane currents to support their functional differences. ⋯ Data presented in this study uncovered pathologies in the IT exhibiting neurons of the IGL and VLG. In conclusion, the data presented here suggest that different subthreshold current expression supports the functional differences of thalamic nuclei. Those differences are promising for possible pharmacological manipulations of specified cell types in pathophysiologies including absence epilepsy.
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The present study generated a novel DNA complex to specifically target endothelial NF-κB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFκB) contains a DNA decoy which inhibits NF-κB activity, and a DNA aptamer (GS-24), a ligand of transferrin receptor (TfR), which allows for targeted delivery of the DNA decoy into cells. ⋯ Intravenous (i.v.) injection of GS24-'NFκB (15mg/kg) was able to inhibit the levels of phoseph-p65 and VCAM-1 in brain endothelial cells in a mouse lipopolysaccharide (LPS)-induced inflammatory model in vivo. In conclusion, our approach using DNA nanotechnology for DNA decoy delivery could potentially be utilized for inhibition of inflammation in ischemic stroke and other neuro-inflammatory diseases affecting cerebral vasculature.