Neuroscience
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The present study was performed to determine neuronal loci and individual molecular mechanisms responsible for remifentanil-induced hyperalgesia. The effect of methylnaltrexone (MNX) on remifentanil-induced behavioral hyperalgesia was assessed to distinguish contributions of the peripheral and/or central nervous system to remifentanil-induced hyperalgesia. Phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) in the dorsal root ganglion (DRG) neurons after remifentanil infusion, and the effect of a p38MAPK inhibitor on remifentanil-induced hyperalgesia were analyzed to investigate involvement of p38MAPK in the peripheral mechanisms of remifentanil-induced hyperalgesia. ⋯ Prodynorphin expression increased in the spinal cord, and a BK2 antagonist inhibited hyperalgesia during the late post-infusion period. Remifentanil-induced exacerbation of incisional hyperalgesia was inhibited by MNX and the BK2 antagonist. The present study demonstrated that remifentanil activates peripheral and spinal neurons to promote chronologically distinctive hyperalgesia. p38MAPK phosphorylation in the DRG neuron leads to peripherally-driven hyperalgesia during the early post-infusion period, while spinal dynorphin-bradykinin signaling promotes hyperalgesia during the late post-infusion period.
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As voluntary muscle fatigue increases, the perception of the effort required to produce a particular level of force also increases. This occurs because we produce greater neural outputs from the brain to compensate for the fatigue-induced loss of force. Muscle fatigue can also be generated following bouts of neuromuscular electrical stimulation (NMES), a technique widely used for rehabilitation and training purposes. ⋯ Contrary to voluntary muscle fatigue, the sense of effort decreased post-NMES in both tasks despite increased neural outputs to the elbow flexors of the fatigued indicator arm. This shows that the relationship between motor command magnitude and effort perception was completely modified by NMES. It is proposed that NMES alters the sensory structures responsible for effort signal integration.
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Up-regulation of proBDNF in ischemic brain and the detrimental role of proBDNF on cellular survival has already been established. We propose that the up-regulated proBDNF may trigger the harmful events and evoke a secondary ischemic damage after ischemia. This study aimed to establish the neuroprotective effects of anti-proBDNF antibody in a rat photothrombotic ischemic model. ⋯ Significant sensorimotor functional improvements were also noticed at 7d after anti-proBDNF treatment. We conclude that anti-proBDNF treatment is anti-apoptotic and anti-inflammatory, and plays advantageous role in promoting cellular growth and improving sensorimotor function after ischemic insult. Taken together, our study suggests that this anti-proBDNF treatment can be considered as a therapeutic approach for ischemic recovery.
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An animal's choice behavior is shaped by the outcome feedback from selected actions in a trial-and-error approach. Tonically active neurons (TANs), presumed cholinergic interneurons in the striatum, are thought to be involved in the learning and performance of reward-directed behaviors, but it remains unclear how TANs are involved in shaping reward-directed choice behaviors based on the outcome feedback. To this end, we recorded activity of TANs from the dorsal striatum of two macaque monkeys (Macaca fuscata; 1 male, 1 female) while they performed a multi-step choice task to obtain multiple rewards. ⋯ Moreover, the feedback responses of TANs were similarly observed in any search trials, without distinctions regarding the predicted probability of rewards and the location of chosen targets. Unambiguously, TANs detected reward and no-reward feedback specifically when the monkeys performed trial-and-error searches, in which the monkeys were learning the value of the targets and adjusting their subsequent choice behavior based on the reward and no-reward feedback. These results suggest that striatal cholinergic interneurons signal outcome feedback specifically during search behavior, in circumstances where the choice outcomes cannot be predicted with certainty by the animals.
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Leukemia inhibitory factor (LIF) has been shown to be involved in myelination. The present study investigated whether LIF plays a significant role in the formation of stress adaptation using stress-adaptive and -maladaptive mice, and also attempted to confirm whether there was any difference in myelination between these animal models. A single exposure to restraint stress for 1 h induced a decrease in head-dipping behavior in the hole-board test. ⋯ On the other hand, major myelin proteins including myelin-associated glycoprotein and myelin basic protein, as well as mature oligodendrocytes, were decreased in the hippocampus of stress-maladaptive, but not stress-adaptive, mice. Furthermore, while the levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) were increased in the hippocampus of stress-adaptive, this change did not occur in stress-maladaptive mice. Taken together, the present findings suggest that LIF, which may be derived from activated astrocytes, plays a critical role in the maintenance of hippocampal myelination via an ERK signaling pathway, and contributes to the development of stress adaptation.