Neuroscience
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Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). ⋯ The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.
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Adrenomedullin (AM) belongs to a calcitonin gene-related peptide (CGRP) family and has been demonstrated to recruit CGRP following chronic use of morphine and neuronal nitric oxide synthase (nNOS) in inflammation. The present study investigated the possibility that AM initiates the changes of other molecules contributing to the development of morphine tolerance in its chronic use. Intrathecal (i.t.) co-administration of the AM receptor antagonist AM22-52 (35.8 μg) inhibited tolerance to morphine-induced analgesia while a daily injection of the AM receptor agonist AM1-50 (8 μg, i.t., bolus) for 9 days induced a decrease in the potency of morphine analgesia and thermal hyperalgesia. ⋯ Particularly, the co-administration of AM22-52 (35.8 μg) inhibited the morphine-induced alterations in nNOS and BAM22. These results indicated that the increase in nNOS and CGRP expressions and the decrease in BAM22 were attributed to the increased AM receptor signaling induced by chronic morphine. The present study supports the hypothesis that the enhancement of AM bioactivity triggered upregulation of pronociceptive mediators and downregulation of pain-inhibiting molecule in a cascade contributing to the development of morphine tolerance.
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Over human leg muscles, three motor responses (MR) can commonly be elicited, namely short-latency reflex (SLR), medium-latency reflex (MLR), and long-latency reflex (LLR). The MLR is less well understood than SLR and LLR. As the response to subsequent stimuli may be used to characterize central influences of an MR, we were interested, whether the MLR differs from SLR and LLR with respect to its habituation and facilitation behavior. ⋯ After train stimuli, the LLR but not SLR and MLR gained significantly in amplitude as compared with single stimuli. Different to SLR and LLR, the MLR showed significant habituation behavior at a stimulus repetition rate of 1Hz but not of 0.4 Hz. Thus, inhibitory interneurons seem to be involved in the MLR pathway.
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Cav2.2 channels are a substrate for phosphorylation by protein kinase C (PKC) isozymes. The contribution of Cavβ, an auxiliary subunit of these channels, in the PKC modulation was studied. Cav2.2 channels were expressed in Xenopus oocytes in various subunit combinations with or without Cavβ subunits. ⋯ The action of PKC on these sites was further substantiated by the increased basal IBa along with the loss of MCh potentiation when Ser/Thr was mutated to aspartate. The observation that MCh or PKC isozymes failed to affect Cav2.2 currents in the presence of Cavβ subunits suggests that these subunits may have interfered with the interaction between PKC and Ser/Thr sites of Cav2.2α1 subunits. In addition to affecting channel expression and current kinetics, Cavβ subunits may also modulate the response of these channels to neurochemicals.
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The rat femoral nerve is a valuable model allowing studies on specificity of motor axon regeneration. Despite common use of this model, the functional consequences of femoral nerve lesions and their relationship to precision of axonal regeneration have not been evaluated. Here we assessed gait recovery after femoral nerve injuries of varying severity in adult female Wistar rats using a video-based approach, single-frame motion analysis (SFMA). ⋯ The results also suggest that MNs' projection patterns may influence their contribution to muscle performance. In addition to the experiments described above, we performed repeated measurements and statistical analyses to validate the SFMA. The results revealed high accuracy and reproducibility of the SFMA measurements.