| 1. |
- Luisa Rojo Antuna, Maria, et al.
(författare)
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Differential adaptive changes on serotonin and noradrenaline transporters in a rat model of peripheral neuropathic pain
- 2012
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Ingår i: Neuroscience Letters. - Ireland : Elsevier. - 0304-3940 .- 1872-7972. ; 515:2, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin and noradrenaline reuptake inhibitors have shown to produce antinociceptive effects in several animal models of neuropathic pain. In the present work, we have analyzed the density of brain and spinal serotonin and noradrenaline transporters (5-HIT and NAT) in a rat model of neuropathic pain, the spinal nerve ligation (SNL). Quantitative autoradiography revealed a significant decrease in the density of 5-HIT ([H-3]citalopram binding) at the level of the lumbar spinal cord following 2 weeks of neuropathic surgery (lamina V. -40%: 6.01 +/- 0.64 nCi/mg tissue in sham-animals vs 3.59 +/- 1.56 in SNL-animals; lamina X, -30%: 9.10 +/- 2.00 vs 6.40 +/- 1.93 and lamina IX, -22%: 12.01 +/- 2.41 vs 9.42 +/- 1.58). By contrast, NAT density ([H-3]nisoxetine binding) was significantly increased (lamina I-II, +34%: 2.20 +/- 0.45 vs 2.96 +/- 0.65; lamina V. +57%: 1.34 +/- 0.28 vs 2.11 +/- 0.66; and lamina IX, +58%: 2.39 0.71 vs 3.78 +/- 1.10). At supraspinal structures, SNL induced adaptive changes only in the density of 5-HIT (septal nuclei, +33%: 10.18 +/- 2.03 vs 13.53 +/- 1.14: CA3 field of hippocampus, +18%: 6.94 +/- 1.01 vs 8.21 +/- 0.81: paraventricular thalamic nucleus, +21%: 15.18 +/- 1.88 vs 18.35 +/- 2.08: lateral hypothalamic area, +40%: 12.68 +/- 1.90 vs 17.8 +/- 2.55: ventromedial hypothalamic nuclei, +19%: 7.16 +/- 0.92 vs 8.55 +/- 0.40; and dorsal raphe nucleus, +15%: 35.22 +/- 3.88 vs 40.68 +/- 13.11). Thus, we demonstrate, in the SNL model of neuropathic pain, the existence of opposite changes in the spinal expression of 5-WIT (down-regulation) and NAT(up-regulation), and the presence of supraspinal adaptive changes (up-regulation) only on 5-HIT density. These findings may help understanding the pathogeny of neuropathic pain and the differential analgesic action of antidepressants targeting 5-HIT and/or NAT transporters. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Thorell, Kaisa, 1983, et al.
(författare)
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The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
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| 3. |
- Vidal, Rebeca, et al.
(författare)
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New strategies in the development of antidepressants : towards the modulation of neuroplasticity pathways
- 2011
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Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 17:5, s. 521-533
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Tidskriftsartikel (refereegranskat)abstract
- Over the past five decades, the pharmacological treatment of depression has been based on the pathophysiological hypothesis of a deficiency in monoamines, mainly serotonin and noradrenaline. Antidepressants prescribed today, all of them designed to enhance central monoaminergic tone, present several important limitations, including a 2-5 weeks response lag and also a limited clinical efficacy. As it is increasingly evident that the abnormalities associated to depression go beyond monoamines, the development of better antide-pressants will depend on the identification and understanding of new cellular targets. In this regard, much evidence supports a role for cellular and molecular mechanisms of neuroplasticity, including neurotrophic inputs, in mood disorders, in parallel with the biological features associated to stress conditions. In order to illustrate the possible relevance of neuroplasticity-related pathways for the therapy of depressive states, we here review the biological evidence supporting some therapeutic strategies in a very initial phase of development (modulation of the Wnt/GSK-3β/β-catenin pathway, potentiation of endocannabinoid activity, agonism of 5-HT4 receptors), which involve modulation of downstream mechanisms and neuroplasticity circuits. These strategies also show the existence of mixed mechanisms of action, constituting a nexus between the "classic" aminergic theory and the "new" neuroplasticity hypothesis.
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| 4. |
- Vidal, Rebeca, et al.
(författare)
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Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?
- 2014
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Ingår i: Current pharmaceutical design. - : Bentham Science Publishers. - 1381-6128 .- 1873-4286. ; 20:23, s. 3751-3762
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.
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| 5. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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