Neuroscience
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Several circulating microRNAs (miRNAs) have been proved to serve as stable biomarkers in blood for acute ischemic stroke (AIS). However, the functions of these biomarkers remain elusive. By conducting the integration analysis of circulating miRNAs and peripheral whole-blood mRNAs using bioinformatics methods, we explored the biological role of these circulating markers in peripheral whole blood at the genome-wide level. ⋯ Finally, we analyzed biological functions of Mo-mRNAs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and constructed networks among the Mo-mRNAs, overlapped M-miRNAs (Mo-miRNAs), and their functions. The Mo-mRNAs were enriched in functions such as platelet degranulation, immune response, and pathways associated with phagosome biology and Staphylococcus aureus infection. This study provides an integrated view of interactions among circulating miRNAs and peripheral whole-blood mRNAs involved in the pathophysiological processes of male AIS.
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While the VGF-derived TLQP peptides have been shown to prevent neuronal apoptosis, and to act on synaptic strengthening, their involvement in Amyotrophic Lateral Sclerosis (ALS) remains unclarified. We studied human ALS patients' plasma (taken at early to late disease stages) and primary fibroblast cultures (patients vs controls), in parallel with SOD1-G93A transgenic mice (taken at pre-, early- and late symptomatic stages) and the mouse motor neuron cell line (NSC-34) treated with Sodium Arsenite (SA) to induce oxidative stress. TLQP peptides were measured by enzyme-linked immunosorbent assay, in parallel with gel chromatography characterization, while their localization was studied by immunohistochemistry. ⋯ In mice, a comparable pattern of reduction was shown (vs wild type), in both plasma and spinal cord already in the pre-symptomatic phase (about 26% and 70%, respectively). Similarly, the levels of TLQP peptides were reduced in ALS fibroblasts (31% of controls) and in the NSC-34 treated with Sodium Arsenite (53% of decrease), however, the exogeneous TLQP-21 improved cell viability (SA-treated cells with TLQP-21, vs SA-treated cells only: about 83% vs. 75%). Hence, TLQP peptides, reduced upon oxidative stress, are suggested as blood biomarkers, while TLQP-21 exerts a neuroprotective activity.
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Clinical Trial
Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.
Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). ⋯ Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders.
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The ability to update position and orientation to reach a goal is crucial to spatial navigation and individuals vary considerably in this ability. The current structural MRI study used voxel-based morphometry (VBM) analysis to relate individual differences in human brain morphology to performance in an active navigation task that relied on updating position and orientation in a landmark-free environment. Goal-directed navigation took place from either a first person perspective, similar to a person walking through the landmark-free environment, or Survey perspective, a bird's eye view. ⋯ Significant structural volume correlations in the hippocampus, entorhinal cortex, and thalamus were related to first person navigational accuracy. Our results support the theory that hippocampus, entorhinal cortex, and thalamus are key structures for updating position and orientation during ground-level navigation. Furthermore, the results suggest that morphological differences in these regions underlie individual navigational abilities, providing an important link between animal models of navigation and the variability in human navigation.
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Replacement of dead neurons following ischemia, either via enhanced endogenous neurogenesis or stem cell therapy, has long been sought. Unfortunately, while various therapies that enhance neurogenesis or stem cell therapies have proven beneficial in animal models, they have all uniformly failed to truly replace dead neurons in the ischemic core to facilitate long-term recovery. Remarkably, we observe robust repopulation of medium-spiny neurons within the ischemic core of juvenile mice following experimental stroke. ⋯ Ablation of neurogenesis using irradiation prevented neuronal replacement and functional recovery in MCAo-injured juvenile mice. In contrast, findings in adults were consistent with previous reports, that newborn neurons failed to mature and died, offering little therapeutic potential. These data provide support for neuronal replacement and consequent functional recovery following ischemic stroke and new targets in the development of novel therapies to treat stroke.