Journal of neuroscience research
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In vivo (1)H NMR spectroscopy at 7 T was utilized to measure the changes in lactate concentration upon repeated identical visual stimuli, each lasting for 2 min. The average amplitude of these increases was found to be reduced over time (P < 0.01), from 0.13 +/- 0.02 micromol/g during the first half of the stimulation paradigm, to 0.06 +/- 0.02 micromol/g during the second half of the stimulation paradigm. ⋯ This finding may suggest a differential adaptation of cortical output that is not reflected at the level of the global excitation-inhibition activity of the cortical canonical circuits. Alternative possibilities that could account for an adaptation of [Lac] changes are also discussed.
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Neuritin is a small, highly conserved GPI-anchored protein involved in neurite outgrowth. We have analyzed the involvement of neuritin in NGF-induced differentiation of PC12 cells by investigating the time-course of neuritin expression, the effects of its overexpression or silencing, and the possible mechanisms of its regulation and action. Real-time PCR analysis has shown that neuritin gene is upregulated by NGF in PC12 cells hours before neurite outgrowth becomes appreciable. ⋯ These data suggest that NGF regulates neuritin expression in PC12 cells via the signaling pathway triggered by NO. This study reports the first evidence that neuritin plays a role in modulating neurite outgrowth during the progression of NGF-induced differentiation of PC12 cells. PC12 cells could be considered a valuable model to unravel the mechanism of action of neuritin on neurite outgrowth. (c) 2007 Wiley-Liss, Inc.
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In this study, we examined whether a competitive AMPA receptor antagonist, NBQX, attenuates mechanical allodynia and hyperexcitability of spinal neurons in remote, caudal regions in persistent central neuropathic pain following spinal cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200-250 g). Mechanical thresholds were measured behaviorally, and the excitability of wide-dynamic-range (WDR) dorsal horn neurons in the lumbar cord (L4-L5) was measured to assess central neuropathicpain. ⋯ The hyperexcitability of WDR neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1 mM), dose dependently (P < 0.05). Regression analysis indicated that at least three molecules of NBQX bond per receptor complex, and are needed to achieve inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that the AMPA receptor plays an important role in behaviors related to the maintenance of central neuropathic pain below the level of spinal cord injury.
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The bed nucleus of the stria terminalis (BST) is a limbic structure involved in regulating the hypothalamic-pituitary-adrenal axis as well as in central cardiovascular control. We report here on cardiovascular effects caused by microinjection of noradrenaline (NA) in the BST of the rat brain and the peripheral mechanisms involved in their mediation. Injection of NA (3, 7, 10, 15, 30, or 45 nmol in 100 nl) in the BST of unanesthetized rats caused long-lasting dose-related pressor and bradycardiac responses. ⋯ The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the selective V(1)-vasopressin antagonist dTyr(CH(2))(5)(Me)AVP, suggesting its mediation by vasopressin release into circulation. The bradycardiac response to NA microinjected into the BST was also abolished by pretreatment with the vasopressin antagonist, indicating its reflex origin. In conclusion, results indicate that microinjection of NA into the BST evokes pressor responses, which are mediated by acute vasopressin release.
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Despite a large body of literature on the nociceptin (NC) opioid system in pain modulation, the mechanism of action of NC remains largely unexplored. Here, we investigated the role and mode of action of the spinal NC system in inflammatory pain. Preemptive intrathecal administration of NC attenuated thermal hyperalgesia and mechanical allodynia in rats with intraplantar complete Freund's adjuvant (CFA) injection. ⋯ Real-time reverse transcription-polymerase chain reaction showed that NC reduced the up-regulation of inducible nitric oxide synthase mRNA but not that of neuronal nitric oxide synthase mRNA in spinal cord segments after CFA. Furthermore, [Nphe1]NC(1-13)NH2, a selective opioid receptor-like 1 (ORL1) receptor antagonist, significantly antagonized the effects of NC on pain modulation and on the expression of inflammatory mediators, indicating a specific NC action through the ORL1 receptor. Together, these findings reveal novel mechanisms by which the NC system produces analgesia.