Neuroscience
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In DRG an increase in miR-133b-3p, miR-143-3p, and miR-1-3p correlates with the lack of development of neuropathic pain following a peripheral nerve injury. Using lentiviral (LV) vectors we found that a single injection of LV-miR-133b-3p or LV-miR-143-3p immediately after a peripheral nerve injury prevented the development of sustained mechanical and cold allodynia. Injection of LV-miR-133b-3p or LV-miR-143-3p by themselves or in combination, on day 3 post-injury produced a partial and transient reduction in mechanical allodynia and a sustained decrease in cold allodynia. ⋯ LV-miR133b-3p and LV-miR-143-3p reduced TRPM8-mRNA. LV-miR-133b-3p and LV-miR-143-3p prevent the development of chronic pain when injected immediately after the injury, but are only partially effective when injected at later times. LV-miR-1a-3p had no effect on pain, but complemented the actions of LV-miR-133b-3p or LV-miR-143-3p resulting in a sustained reversal of pain when co-injected 3 days following nerve injury.
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Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels (ASIC) are heteromeric channels expressed in muscle sensory neurons that detect decreases in pH. We have previously shown ASIC3 is important in activity-induced hyperalgesia. ⋯ There was a significant leftward shift in the pH dose response of steady-state desensitization and decrease in pH-evoked current amplitudes. These results suggest that blockade of ASIC1a modulates the kinetics of heteromeric ASICs to prevent development of activity-induced hyperalgesia. These data suggest ASIC1a is a key subunit in heteromeric ASICs and may be a pharmacological target for treatment of musculoskeletal pain.
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Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP. Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic populations. ⋯ By 24 h, synaptic respiration is significantly impaired compared to synaptic sham, whereas non-synaptic respiration does not decline significantly until 48 h. Decreases in respiration are associated with increases in oxidative damage to synaptic and non-synaptic mitochondrial proteins at 48 h and 72 h, respectively. These results indicate that the therapeutic window for mitochondria-targeted pharmacological neuroprotectants to prevent respiratory dysfunction is shorter for the more vulnerable synaptic mitochondria than for the non-synaptic population.
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In this study, fused electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) techniques were utilized to examine the relationship between the ERP (event-related potential) component P300 and fNIRS hemodynamic signals for high-accuracy deception detection. During the performance of a modified concealed information test (CIT) task, a series of Chinese names were presented, which served as the target, irrelevant, or the probe stimuli for both the guilty and innocent groups. For participants in the guilty group, the probe stimulus was their individual name, whereas for the innocent group, the probe stimulus was one irrelevant name. ⋯ Interestingly, we discovered that for the guilty group, the probe stimulus elicited significantly higher P300 amplitude at parietal site and also evoked significantly stronger oxyhemoglobin (HbO) concentration changes in the bilateral superior frontal gyrus and bilateral middle frontal gyrus than the irrelevant stimuli. However, this is not the case for the innocent group, in which participants exhibited no significant differences in both ERP and fNIRS measures between the probe and irrelevant stimuli. More importantly, our findings also demonstrated that the combined ERP and fNIRS feature was able to differentiate the guilty and innocent groups with enhanced sensitivity, in which AUC (the area under Receiver Operating Characteristic curve) is 0.94 for deception detection based on the combined indicator, much higher than that based on the ERP component P300 only (0.85) or HbO measure only (0.84).
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Prior research with a rat model of behavioral therapy [i.e., effort-based reward (EBR) contingency training] suggests that strengthened associations between physical effort and desired outcomes enhance neurobiological indices of resilience. In the current study, male and female Long-Evans rats were exposed to either six weeks of EBR training or noncontingent training prior to 10 days of exposure to chronic unpredictable stress (CUS). Subsequently, all animals were exposed to a problem-solving task and then trained in a spatial learning/foraging task, the Dry Land Maze (DLM). ⋯ Contingency training decreased BDNF-immunoreactivity (ir) in the hippocampus CA1 and lateral habenula, implicating differential neuroplasticity responses in the training groups. Further, coordinated fos-ir activation in areas associated with emotional resilience (i.e., motivation-regulation) was observed in contingent-trained animals. In sum, the current findings confirm that behavioral training is associated with neurobiological markers of emotional resilience; however, further assessments are necessary to more accurately determine the therapeutic potential for the EBR contingency training model.