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| 2. |
- Agosti, Francina, et al.
(author)
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Melanocortin 4 receptor activation inhibits presynaptic N-type calcium channels in amygdaloid complex neurons
- 2014
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 40:5, s. 2755-2765
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Journal article (peer-reviewed)abstract
- The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor involved in food intake and energy expenditure regulation. MC4R activation modifies neuronal activity but the molecular mechanisms by which this regulation occurs remain unclear. Here, we tested the hypothesis that MC4R activation regulates the activity of voltage-gated calcium channels and, as a consequence, synaptic activity. We also tested whether the proposed effect occurs in the amygdala, a brain area known to mediate the anorexigenic actions of MC4R signaling. Using the patch-clamp technique, we found that the activation of MC4R with its agonist melanotan II specifically inhibited 34.5 +/- 1.5% of N-type calcium currents in transiently transfected HEK293 cells. This inhibition was concentration-dependent, voltage-independent and occluded by the G(s) pathway inhibitor cholera toxin. Moreover, we found that melanotan II specifically inhibited 25.9 +/- 2.0% of native N-type calcium currents and 55.4 +/- 14.4% of evoked inhibitory postsynaptic currents in mouse cultured amygdala neurons. Invivo, we found that the MC4R agonist RO27-3225 increased the marker of cellular activity c-Fos in several components of the amygdala, whereas the N-type channel blocker conotoxin GVIA increased c-Fos expression exclusively in the central subdivision of the amygdala. Thus, MC4R specifically inhibited the presynaptic N-type channel subtype, and this inhibition may be important for the effects of melanocortin in the central subdivision of the amygdala.
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| 3. |
- Baczyk, Marcin, et al.
(author)
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Facilitation of ipsilateral actions of corticospinal tract neurons on feline motoneurons by transcranial direct current stimulation
- 2014
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X. ; 40:4, s. 2628-2640
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Journal article (peer-reviewed)abstract
- Ipsilateral actions of pyramidal tract (PT) neurons are weak but may, if strengthened, compensate for deficient crossed PT actions following brain damage. The purpose of the present study was to examine whether transcranial direct current stimulation (tDCS) can strengthen ipsilateral PT (iPT) actions; in particular, those relayed by reticulospinal neurons co-excited by axon collaterals of fibres descending in the iPT and contralateral PT (coPT) and of reticulospinal neurons descending in the medial longitudinal fascicle (MLF). The effects of tDCS were assessed in acute experiments on deeply anaesthetized cats by comparing postsynaptic potentials evoked in hindlimb motoneurons and discharges recorded from their axons in a ventral root, before, during and after tDCS. tDCS was consistently found to facilitate joint actions of the iPT and coPT, especially when they were stimulated together with the MLF. Both excitatory postsynaptic potentials and inhibitory postsynaptic potentials evoked in motoneurons and the ensuing ventral root discharges were facilitated, even though the facilitatory effects of tDCS were not sufficient for activation of motoneurons by iPT neurons alone. Facilitation outlasted single tDCS periods by at least a few minutes, and the effects evoked by repeated tDCS by up to 2 h. The results of this study thus indicate that tDCS may increase the contribution of iPT actions to the recovery of motor functions after injuries to coPT neurons, and thereby assist rehabilitation, provided that corticoreticular and reticulospinal connections are preserved.
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| 5. |
- Berube-Carriere, Noemie, et al.
(author)
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Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons
- 2012
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 35:4, s. 527-538
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Journal article (peer-reviewed)abstract
- Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual THVGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
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| 7. |
- Björkman, Anders, et al.
(author)
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Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.
- 2012
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In: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 2098-2106
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Journal article (peer-reviewed)abstract
- Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.
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| 8. |
- Block, Linda, et al.
(author)
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Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes.
- 2013
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In: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 38:11, s. 3669-3678
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Journal article (peer-reviewed)abstract
- Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na(+) channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, <10(-8) m, evoked Ca(2+) transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca(2+) signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, <10(-8) m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca(2+) signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist.
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| 9. |
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| 10. |
- Clausen, Fredrik, et al.
(author)
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Neutralization of interleukin-1 beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice
- 2011
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 34:1, s. 110-123
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Journal article (peer-reviewed)abstract
- Increasing evidence suggests that interleukin-1 beta (IL-1 beta) is a key mediator of the inflammatory response following traumatic brain injury (TBI). Recently, we showed that intracerebroventricular administration of an IL-1 beta-neutralizing antibody was neuroprotective following TBI in mice. In the present study, an anti-IL-1 beta antibody or control antibody was administered intraperitoneally following controlled cortical injury (CCI) TBI or sham injury in 105 mice and we extended our histological, immunological and behavioral analysis. First, we demonstrated that the treatment antibody reached target brain regions of brain-injured animals in high concentrations (> 11 nm) remaining up to 8 days post-TBI. At 48 h post-injury, the anti-IL-1b treatment attenuated the TBI-induced hemispheric edema (P < 0.05) but not the memory deficits evaluated using the Morris water maze (MWM). Neutralization of IL-1 beta did not influence the TBI-induced increases (P < 0.05) in the gene expression of the Ccl3 and Ccr2 chemokines, IL-6 or Gfap. Up to 20 days post-injury, neutralization of IL-1 beta was associated with improved visuospatial learning in the MWM, reduced loss of hemispheric tissue and attenuation of the microglial activation caused by TBI (P < 0.05). Motor function using the rotarod and cylinder tests was not affected by the anti-IL-1 beta treatment. Our results suggest an important negative role for IL-1 beta in TBI. The improved histological and behavioral outcome following anti-IL-1 beta treatment also implies that further exploration of IL-1 beta-neutralizing compounds as a treatment option for TBI patients is warranted.
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