Neuroscience
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The vestibular system of the inner ear contains Type I and Type II hair cells (HCs) generated from sensory progenitor cells; however, little is known about how the HC subtypes are formed. Sox2 (encoding SRY-box 2) is expressed in Type II, but not in Type I, HCs. The present study aimed to investigate the role of SOX2 in cell fate determination in Type I vs. ⋯ These results demonstrate that SOX2 plays a critical role in the determination of Type II vs. Type I HC fate. The results suggested that Sox2 is a potential target for generating Type I HCs, which may be important for regenerative strategies for balance disorders.
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Dystonia is a disabling neurological syndrome characterized by abnormal movements and postures that result from intermittent or sustained involuntary muscle contractions; mutations of DYT1/TOR1A are the most common cause of childhood-onset, generalized, inherited dystonia. Patient and mouse model data strongly support dysregulation of the nigrostriatal dopamine neurotransmission circuit in the presence of the DYT1-causing mutation. ⋯ We found that over-expression of mutant torsinA in MSNs produces complex cell-autonomous and non-cell autonomous alterations in nigrostriatal dopaminergic and intrastriatal cholinergic function, similar to that found in pan-cellular DYT1 mouse models. These data introduce targets for future studies to identify which are causative and which are compensatory in DYT1 dystonia, and thereby aid in defining appropriate therapies.
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K-complexes are important transient bio-signal waveforms in sleep stage 2. Detecting k-complexes visually requires a highly qualified expert. In this study, an efficient method for detecting k-complexes from electroencephalogram (EEG) signals based on fractal and frequency features coupled with an ensemble model of three classifiers is presented. ⋯ Comparisons were also made with existing k-complexes detection approaches for which the same datasets were used. The results demonstrate that the proposed approach is efficient in identifying the k-complexes in EEG signals; it yields optimal results with a window size 0.5 s. It can be an effective tool for sleep stages classification and can be useful for doctors and neurologists for diagnosing sleep disorders.
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A stroke-like event follows seizures which may be responsible for the postictal state and a contributing factor to the development of seizure-induced brain abnormalities and behavioral dysfunction associated with epilepsy. Caffeine is the world's most popular drug with ∼85% of people in the USA consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their body and brain during seizures. ⋯ Likewise, the specific A2A receptor antagonist, SCH-58261, mimicked caffeine by causing a significant drop in pre-seizure pO2 and the area and time below the severe hypoxic threshold. Moreover, the A2A receptor agonist, CGS-21680 was able to prevent the effect of both caffeine and SCH-58261 adding further evidence that caffeine is likely acting through the A2A receptor. Clinical tracking and investigations are needed to determine the effect of caffeine on postictal symptomology and blood flow in persons with epilepsy.
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Growing evidence indicates that early-life inflammation has adverse effects on adult hippocampal neurogenesis and GABA system. Based the report that hippocampal GABA system is a key modulator in adult hippocampal neurogenesis, the aim of this study was to investigate whether and how early inflammation affects GABAergic system resulting in the alterations of adult hippocampal neurogenesis and related behaviors. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days (PND) 3-5. ⋯ Additionally, postnatal LPS treatment resulted in the activation of astrocytes and the increase expression of toll-like receptor 4 (TLR4) in the second postnatal week and the downregulation of BDNF-TrkB pathway in adulthood. The treatment with TLR4 inhibitor TAK-242 restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in LPS mice via improving GABAAR. The results indicate that postnatal LPS exposure impairs adult hippocampal neurogenesis and causes depression-like behaviors through early astrocytes activation triggering the later GABAAR downregulation.