Neuroscience
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The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. ⋯ This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and-pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1-/- than in PKR2-/- mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics.
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Electroencephalography (EEG) as a biomarker of neuromodulation by High Definition transcranial Direct Current Stimulation (HD-tDCS) offers promise as both techniques are deployable and can be integrated into a single head-gear. The present research addresses experimental design for separating focal EEG effect of HD-tDCS in the '4-cathode × 1-anode' (4 × 1) montage over the left motor area (C3). We assessed change in offline EEG at the homologous central (C3, C4), and occipital (O1, O2) locations. ⋯ For the active arm, similar but less pronounced changes occurred in the alpha band. In contrast, responses to IPS developed similar asymmetric amplitude increase at four harmonics of the IPS of 3 Hz only in the active arm, against a background of a brain-wide symmetric increase in both active and sham arms. Our protocols and analyses suggest methodological caveats for how EEG of tDCS studies could be conducted to isolate putative brain polarization outcomes.
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Increasing evidence suggests that long-term opioids and pain induce similar adaptive changes in the brain's reward circuits, however, how pain alters the addictive properties of opioids remains poorly understood. In this study using a rat model of morphine self-administration (MSA), we found that short-term pain, induced by an intraplantar injection of complete Freund's adjuvant (CFA), acutely decreased voluntary morphine intake, but not food intake, only at a morphine dose that did not affect pain itself. Pre-treatment with indomethacin, a non-opioid inhibitor of pain, before the pain induction blocked the decrease in morphine intake. ⋯ Furthermore, viral overexpression of GluA1 protein in CeA maintained morphine intake at a higher level than controls and reversed the pain-induced reduction in morphine intake. These findings suggest that CeA GluA1 promotes opioid use and its upregulation is sufficient to increase opioid consumption, which counteracts the acute inhibitory effect of pain on opioid intake. These results demonstrate that the CeA GluA1 is a shared target of opioid and pain in regulation of opioid use, which may aid in future development of therapeutic applications in opioid abuse.
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High-intensity cardiovascular exercise prior to motor skill practice is postulated to enhance motor memory consolidation (offline learning), whereas moderate-intensity bouts may benefit skill acquisition (online learning). This study aimed at investigating this suggested intensity-dependent effect of exercise in a complex whole-body task. 50 healthy young adults were randomized into one of three groups performing a bout of either (1) high-intense, (2) moderate-intense, or (3) minimal-intense cycling for a total of 17 min immediately prior to skill practice. The motor task required participants to balance on a tiltable platform (stabilometer) for 30 s. ⋯ Contrary to previous reports, the present data do not support an intensity-dependent effect on motor learning, when exercise is performed prior to task practice. One reason for this might be that similar muscle groups were involved in exercise and the motor task, potentially causing fatigue or interference effects. Further, the results indicate that the memory-promoting effects of acute exercise are task-dependent and may not apply equally for motor skills of different levels of complexity.
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Neuroinflammation has been implicated in the mechanism underlying the progression of neurodegeneration and infectious neuropathology. Growing evidence suggest that hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the main polyphenols presented in extra virgin olive oil (EVOO), has shown potential anti-inflammatory and neuroprotective effects. However, the potential anti-neuroinflammation activity and underlying mechanism of HT remain poorly understood. ⋯ Moreover, HT suppressed the LPS-induced Toll like receptor 4 (TLR4) in BV2 microglia. In vivo administration of HT following LPS injection significantly reduced some proinflammatory mediator levels and microglia/astrocyte activation in the brain. Together, these results suggest that HT suppressed the LPS-induced neuroinflammatory responses via modulation of microglia M1/M2 polarization and downregulation of TLR-4 mediated NF-κB activation and ERK signaling pathway.