Neuroscience
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Human rhythmic movements spontaneously entrain to external rhythmic stimuli. Such sensory-motor entrainment can attract movements to different tempi and enhance their efficiency, with potential clinical applications for motor rehabilitation. Here we investigate whether entrainment of self-paced rhythmic movements can be induced via transcranial alternating current stimulation (tACS), which uses alternating currents to entrain spontaneous brain oscillations at specific frequencies. ⋯ The comparison of participants' movement frequency, amplitude, variability, and phase synchrony with and without tACS failed to reveal entrainment or movement modifications across the two experiments. However, significant differences in stimulation-related side effects reported by participants were found between the two experiments, with phosphenes and burning sensations principally occurring in Experiment 2, and metallic tastes reported marginally more often in Experiment 1. Although other stimulation protocols may be effective, our results suggest that rhythmic movements such as pendulum swinging or locomotion that are low in goal-directedness and/or strongly driven by peripheral and mechanical constraints may not be susceptible to modulation by tACS.
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Nuclear pore complexes (NPCs) play important roles in traffic of molecules between the nucleus and cytoplasm, aberrant distributions of components of NPCs were demonstrated in C9orf72 amyotrophic lateral sclerosis (C9-ALS) patients, but it is elusive whether such abnormities are also the case with other cause of ALS disease. In the present study, we investigated the spatiotemporal distributions of RanGAP1 and 4 representative nucleoporins (GP210, NUP205, NUP107 and NUP50) of NPCs in human Cu/Zn superoxide dismutase-1 mutation transgenic (SOD1-Tg) mice and sporadic ALS patients. ⋯ Furthermore, RanGAP1, GP210 and NUP50 showed similarly abnormal nuclear precipitations and cytoplasmic upregulations in SOD1-Tg mice and ALS patients, moreover, aberrant co-localizations of RanGAP1 with TDP-43 and NUP205 with TDP-43 were also observed in motor neurons. The present study indicated that the mislocalization of these proteins of NPCs may underlie the pathogenesis of ALS both in SOD1-Tg mice and human sporadic ALS patients, and these dysfunctions may be a fundamental pathway for ALS that is not specific only in C9-ALS but also in SOD1-ALS, which may be amenable to pharmacotherapeutic intervention.
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Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cell homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions. ⋯ Besides, multiple cells co-expressed OPN and MTs. Granular OPN signals were detected in secretory vesicles of Golgy (αvβ3 neurons) and in patches adjacent to the plasma membrane (subventricular zone). The findings imply that in demyelinating lesions are generated proteolytic OPN fragments and that OPN/MT interactions contribute to tissue remodeling during an autoimmune attack.
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The neural extracellular matrix (ECM) plays an important role in regulation of perisomatic GABAergic inhibition and synaptic plasticity in the hippocampus and cortex. Decreased labeling of perineuronal nets, a form of ECM predominantly associated with parvalbumin-expressing interneurons in the brain, has been observed in post-mortem studies of schizophrenia patients, specifically, in brain areas such as prefrontal cortex, entorhinal cortex, and amygdala. Moreover, glial ECM in the form of dandelion clock-like structures was reported to be altered in schizophrenia patients. ⋯ Moreover, we found an increased expression of CS56 immunoreactive form of ECM. Importantly, the loss of perineuronal nets was revealed in the mPFC, and was not detected in the hippocampus, suggesting regional specificity of ECM alterations. These data open an avenue for further investigations of functional importance of ECM abnormalities in schizophrenia as well as for search of treatments for their compensation.
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Apocynin (APO) is a well-known NADPH oxidase (NOX) inhibitor. However, several studies have reported its ability to increase glutathione (GSH) levels. Due to GSH is a major non-enzymatic antioxidant in brain, the aim of this study was to evaluate, in the striatum of control and quinolinic acid (QUIN) injected rats, the effect of APO administration on: (1) GSH levels, (2) activity of some enzymes involved in the GSH metabolism, and (3) nuclear factor erythroid-2-related factor 2 (Nrf2) mRNA levels. ⋯ In control rats, APO treatment increased GSH and Nrf2 mRNA levels and the activities of gamma-glutamylcysteine ligase (γ-GCL), glutathione-S-transferase (GST) and glutathione peroxidase (GPx). On the other hand, APO treatment prevented the QUIN-induced decrease in GSH and Nrf2 levels, and in γ-GCL and GPx activities. These data indicate that APO is able to increase GSH levels and the activity of proteins involved in its metabolism, which could be associated with its ability to increase the Nrf2 mRNA levels.