Neuroscience
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Cellular mechanisms underlying the antinociceptive properties of orexins, a group of neuropeptides produced by the hypothalamus, in the spinal dorsal horn have not been thoroughly investigated. We examined how orexin B affects spontaneous synaptic transmission in lamina II neurons, which play a pivotal role in regulating nociceptive transmission, by applying a whole-cell patch-clamp technique to lamina II neurons in adult rat spinal cord slices. In 66% of neurons tested, bath-applied orexin B concentration dependently produced an inward current at -70 mV and/or increased the frequency of glutamatergic spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude, in a manner resistant to the voltage-gated Na+-channel blocker tetrodotoxin (TTX). ⋯ These results indicate that orexin B produces membrane depolarization and/or increased spontaneous l-glutamate release in lamina II neurons by activating orexin-2 receptors, leading to increased excitability of these neurons. Such increases potentially produce an action potential, resulting in enhancement of glycinergic transmission in lamina II neurons. This activity of orexin B, and possibly orexin A, may contribute to its antinociceptive effects, which are partly shared by oxytocin.
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Oxidative stress secondary to excitotoxicity is a common factor in the physiopathology of a variety of neurological disorders. In response to oxidative stress, several signaling pathways, such as MAPK, are activated or inactivated. Mitogen-activated protein kinase (MAPK) family activation must be finely regulated in time and intensity, as this pathway may either preserve cell survival or promote cell death. ⋯ No significant difference in p38 activation with QUIN was observed. QUIN (120 and 240 nmol) decreased BDNF/TrkB levels at 7 days post-injury. JNK inhibition (by an intracerebroventricular injection of SP600125) prevented the QUIN-induced reduction in BDNF and TrkB at 7 day post-injury, suggesting a role for the QUIN-induced JNK activation on the observed decrease in BDNF levels.
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Inflammation and pain are major clinical burdens contributing to multiple disorders and limiting the quality of life of patients. We previously reported that brain electrical stimulation can attenuate joint inflammation in experimental arthritis. Here, we report that non-aversive electrical stimulation of the locus coeruleus (LC), the paraventricular hypothalamic nucleus (PVN) or the ventrolateral column of the periaqueductal gray matter (vlPAG) decreases thermal pain sensitivity, knee inflammation and synovial neutrophilic infiltration in rats with intra-articular zymosan. ⋯ The duration of the tonic immobility increases the control of pain and inflammation. These results reveal survival behavioral and neuromodulatory mechanisms conserved in different species to control pain and inflammation in aversive life-threatening conditions. Our results also suggest that activation of the LC, PVN, or vlPAG by non-invasive methods, such as physical exercise, meditation, psychological interventions or placebo treatments may reduce pain and joint inflammation in arthritis without inducing motor or behavioral alterations.
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RhoA signaling pathway inhibitors such as Y27632 (a ROCK inhibitor) have recently been applied as treatments for spinal cord injury (SCI) because they promote neurite outgrowth and axonal regeneration in neurons. β-Elemene, a compound that is extracted from a natural plant (Curcuma zedoary), influences the expression level of RhoA protein. Whether it can promote neurite outgrowth in motor neurons or enhance locomotor recovery in SCI remains unclear. Here, we initially demonstrated that β-elemene promotes neurite outgrowth of ventral spinal cord 4.1 (VSC4.1) motoneuronal cells and primary cortical neurons. ⋯ BBB scores showed β-elemene significantly promotes locomotor behavioral recovery. In addition, western blotting assays and immunofluorescence staining demonstrated that the expression level of GAP-43 is upregulated by β-elemene treatment in vivo. Thus, our study provided an encouraging novel strategy for the potential treatment of SCI patients with β-elemene.
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There is a large inter-individual variation for umami taste perception. However the neural mechanism for this variability is not well understood. This study investigated brain responses to umami and salty taste among individuals with different umami identification abilities and the effect of repeated oral umami exposure on umami identification and neural processing of taste perceptions. ⋯ In addition, umami identification was significantly improved after umami training for LT. However, it was not reflected in changes in neural activation. The current study shows that attention and association/memory related brain structures play a significant role in the perception of umami taste; and with reference to the results of repeated umami exposure, the presence of very subtle changes regarding the neural processing.