Neuroscience
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Obstructive sleep apnea (OSA), characterized by low arterial oxygen saturation during sleep, is associated with an increased risk of orofacial pain. In this study, we simulated chronic intermittent hypoxia (CIH) during the sleep/rest phase (light phase) to determine the role of transient receptor potential vanilloid 1 (TRPV1) in mediating enhanced orofacial nocifensive behavior and trigeminal spinal subnucleus caudalis (Vc) neuronal responses to capsaicin (a TRPV1 agonist) stimulation in a rat model of OSA. Rats were subjected to CIH (nadir O2, 5%) during the light phase for 8 or 16 consecutive days. ⋯ Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive cells intermingled with the central terminal of TRPV1-positive afferents in the Vc. The number of pERK-immunoreactive cells following low-dose capsaicin (0.33 µM) application to the tongue was significantly greater in the middle portion of the Vc of CIH rats than of normoxic rats and recovered under normoxic conditions after CIH. These data suggest that CIH during the sleep (light) phase is sufficient to transiently enhance pain on the ocular surface and intraoral mucosa via TRPV1-dependent mechanisms.
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Analysis of the basal ganglia has been important in investigating the effects of Parkinson's disease as well as treatments for Parkinson's disease. One method of analysis has been using MRI for non-invasively segmenting the basal ganglia, then investigating significant parameters that involve the basal ganglia, such as fiber orientations and positional markers for deep brain stimulation (DBS). Following enhancements to optimizations and improvements to 3T and 7T MRI acquisitions, we utilized Lead-DBS on human connectome project data to automatically segment the basal ganglia of 49 human connectome project subjects, reducing the reliance on manual segmentation for more consistency. ⋯ Tractography streamlines generated between basal ganglia structures using 3T images showed less standard deviation in streamline count than using 7T images. Mean tractography streamline counts generated using 3T diffusion images were all higher in count than streamlines generated using 7T diffusion images. We illustrate a potential method for analyzing the structural connectivity between basal ganglia structures, as well as visualize possible differences in probabilistic tractography that can arise from different acquisition protocols.
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Proactive and reactive brain activities usually refer to processes occurring in anticipation or in response to perceptual and/or cognitive events. Previous studies found that, in auditory tasks, musical expertise improves performance mainly at the reactive stage of processing. In the present work, we aimed at acknowledging the effects of musical practice on proactive brain activities as a result of neuroplasticity processes occurring at the level of anticipatory motor/cognitive functions. ⋯ In the reactive stage of processing (i.e., following stimulus presentation), musicians showed enhanced early (N1) and late (P3) components, in line with longstanding literature of enhanced auditory processing in this group. Crucially, we also found a significant correlation between the N1 component and years of musical practice. We interpreted these findings in terms of neural plasticity processes resulting from musical training, which lead musicians to high efficiency in auditory sensorial anticipation and more intense cognitive control and sound analysis.
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Activation of epidermal growth factor receptor (EGFR) tyrosine kinase is associated with increased extracellular signal-regulated kinase (ERK) 1/2 signaling in the hypothalamic paraventricular nucleus (PVN), which contributes to the sympathetic excitation in heart failure (HF). Transforming growth factor (TGF)-α is a major endogenous ligand for EGFR. The present study sought to determine whether TGF-α increases in the PVN in HF and promotes the activation of EGFR to increase ERK1/2 activity. ⋯ Furthermore, bilateral PVN microinjection of a TGF-α siRNA in HF rats significantly decreased the elevated levels of TGF-α, p-EGFR, p-ERK1/2 and the mRNA expression of PICs and RAS components in the PVN, compared with the HF rats treated with a scrambled siRNA. The TGF-α siRNA-treated HF rats also exhibited lower plasma norepinephrine levels and improved peripheral manifestations of HF. These data suggest that TGF-α expression is upregulated in the PVN in HF and induces the activation of EGFR-mediated ERK1/2 signaling to augment the inflammation and RAS activity that drives sympathetic excitation in HF.
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FK501 binding protein 51 (FKBP5) is a stress response prolyl isomerase that inhibits the translocation of the glucocorticoid receptor (GR) heterocomplex to the nucleus. Previous studies have shown that the expression levels of FKBP5 are positively correlated with psychiatric disorders, including depression and post-traumatic stress disorder. In rodents, FKBP5 deletion in the brain leads to be resilient to stress-induced depression. ⋯ In the hippocampus, GR activation alters the release probability in inhibitory synapses as well as the postsynaptic contribution of glutamate receptors in excitatory synapses; however, no such alterations were induced in the absence of FKBP5. FKBP5 deficiency causes insensitivity to activated GRs in the hippocampus suggesting that FKBP5 mediates synaptic changes caused by GR activation. Our study provides electrophysiological evidence of stress resilience observed in FKBP5-deficient mice.