Neuroscience
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The N-methyl-d-aspartate receptor (NMDAR) has been strongly implicated in mechanisms of persistent pain states. The purpose of the present study was to determine whether the NMDAR NR-1, a key subunit in regulation of NMDAR channel complex is directly contributing to the onset and propagation of peripheral nerve injury-induced allodynia and whether N-methyl-d-aspartate (NMDA) signaling interacts with spinal chemokine (chemotactic cytokines) expression and glial activation. We used genetically engineered male mice that had their normal NR1 gene knocked out and expressed a modified NR1 gene at either normal level (NR1 +/+, wild type) or at a low level (NR1+/-, knock down). ⋯ There were no apparent differences in microglial or astrocytic expression between the wild type and knock down mice. These data provide important insights into the cascade of events involving the dynamic interaction between NMDAR function and spinal chemokine and glial production in neuropathic pain states. The results support the findings that chemokine signaling releases glutamate in the spinal cord.
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Transient receptor potential-vanilloid type-1 (TRPV1) is a ligand-gated cation channel with preference for divalent cations, especially Ca(2+) (sequence of conductances: Ca(2+)>Mg(2+)>Na(+) approximately/= K(+) approximately/= Cs(+)). In the present study, the two-electrode voltage-clamp technique was used on oocytes of Xenopus laevis expressing TRPV1 to evaluate whether human TRPV1 also conducts protons. In medium devoid of K(+), Na(+), Mg(2+), and Ca(2+), capsaicin 1 microM induced a significant inward current (62% of the current in physiological medium). ⋯ The same current was also demonstrated in Chinese hamster ovary cells expressing human TRPV1. We conclude that TRPV1 conducts protons, in addition to Na(+), K(+), Mg(2+), and Ca(2+). The proton conductance may help to initiate action potentials and to translocate H(+) dependent on TRPV1 activation and membrane potential.
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Comparative Study
The hypothalamic-pituitary-adrenal and glucose responses to daily repeated immobilisation stress in rats: individual differences.
It is accepted that there are important individual differences in the vulnerability to stress-induced pathologies, most of them associated to the hypothalamic-pituitary and sympatho-medullo-adrenal axes, the two prototypical stress-responsive systems. However, there are few studies specifically aimed at characterising individual differences in the physiological response to daily repeated stress in rats. In the present work, male rats were submitted to repeated immobilisation (IMO) stress (1 h daily for 13 days) and several samples were taken at specific days and time points. ⋯ When the animals were classified in three groups on the basis of their plasma ACTH levels immediately after the first immobilisation, individual differences in the ACTH response progressively disappeared on successive exposures to the stressor, whereas those in corticosterone and glucose were more sustained. The present results suggest that there are individual differences in the physiological response to stress that tend to be reduced rather than accentuated by repeated exposure to the stressor. Nevertheless, this buffering effect of repeated stress was dependent on the particular variable studied.
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Prevention of neuronal apoptosis has been introduced as a new therapeutic strategy for neurodegenerative disorders. We have previously reported anti-apoptotic effects of transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine, in models of cerebral ischemia and in cultured neurons and recently focused on the mechanisms underlying the anti-apoptotic effect of TGF-beta1. The anti-apoptotic transcriptional factor nuclear factor kappa B (NF-kappaB) shows high impact in the cell survival function of multiple cytokines and growth factors. ⋯ TGF-beta1 produced a concomitant increase in the phosphorylations of Ikappabeta kinase (IKKalpha/beta) and Ikappabetaalpha with a subsequent degradation of Ikappabetaalpha. Interestingly, the increased phosphorylation of IKKalpha/beta and Ikappabetaalpha was abrogated by wortmannin, but not by U0126, suggesting that PI3k/Akt and MAPK/Erk1,2 pathways triggered by TGF-beta1 regulated the activation of NF-kappabeta through different mechanisms. Of note, wortmannin and U0126, as well as kappabeta-decoy DNA, abolished the anti-apoptotic effect of TGF-beta1, corroborating the notion that both PI3k/Akt and MAPK/Erk1,2 pathways, and NF-kappabeta activity are necessary for the anti-apoptotic activity of TGF-beta1.
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In seven freely moving squirrel monkeys (Saimiri sciureus), the neuronal activity in the periaqueductal gray (PAG) and bordering structures was registered during vocal communication, using a telemetric single-unit recording technique. In 9.3% of the PAG neurons, a vocalization-correlated activity was found. Four reaction types could be distinguished: a) neurons, showing an activity burst immediately before vocalization onset; b) neurons, firing during vocalization, and starting shortly before vocalization onset; c) neurons, firing exclusively during vocalization; d) neurons, firing in the interval between perceived vocalizations (i.e. vocalizations produced by group mates) and self-produced vocal response. ⋯ None of the neurons reflected simple acoustic parameters, such as fundamental frequency or amplitude, in its discharge rate. None of the neurons reacted to vocalizations of other animals not responded to by the experimental animal. All four reaction types found in the PAG were also found in the reticular formation bordering the PAG, though in lower density.