1. |
- Basic, Dean, et al.
(författare)
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Changes in regional brain monoaminergic activity and temporary down-regulation in stress response from dietary supplementation with L-tryptophan in Atlantic cod (Gadus morhua)
- 2013
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 109:12, s. 2166-2174
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Tidskriftsartikel (refereegranskat)abstract
- The brain monoamines serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) both play an integrative role in behavioural and neuroendocrine responses to challenges, and comparative models suggest common mechanisms for dietary modulation of transmission by these signal substances in vertebrates. Previous studies in teleosts demonstrate that 7 d of dietary administration with L-tryptophan (Trp), the direct precursor of 5-HT, suppresses the endocrine stress response. The present study investigated how long the suppressive effects of a Trp-enriched feed regimen, at doses corresponding to two, three or four times the Trp levels in commercial feed, last in juvenile Atlantic cod (Gadus morhua) when the fish are reintroduced to a diet with standard amino acid composition. We also wanted to determine whether Trp supplementation induced changes in brain monoaminergic neurochemistry in those forebrain structures innervated by DA- and 5-HTergic neurons, by measuring regional activity of DA and 5-HT in the lateral pallial regions (Dl) of the telencephalon and nucleus lateralis tuberis (NLT) of the hypothalamus. Dietary Trp resulted in a dose-dependent suppression in plasma cortisol among fish exposed to confinement stress on the first day following experimental diet; however, such an effect was not observed at 2 or 6 d after Trp treatment. Feeding the fish with moderate Trp doses also evoked a general increase in DA and 5-HT-ergic activity, suggesting that these neural circuits within the NLT and Dl may be indirectly involved in regulating the acute stress response.
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2. |
- Basic, Dean, et al.
(författare)
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Short- and long-term effects of dietary L-tryptophan supplementation on the neuroendocrine stress response in seawater-reared Atlantic salmon (Salmo salar)
- 2013
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Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 388, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- The essential amino acid L-tryptophan (Trp) is the immediate precursor of the neurotransmitter serotonin (5-HT). Supplementing Trp through diet has been shown to suppress the neuroendocrine stress response in vertebrates including teleosts. In salmonid fish, adjusting to the social environment as well as habituation to seawater involves the neuroendocrine stress response, suggesting that such environmental factors may modulate the stress-reducing effects of Trp. To date, studies that have investigated the neuroendocrine effects of dietary Trp have only been conducted in rainbow trout (Oncorhynchus mykiss), a salmonid species, under conditions featuring social isolation in the freshwater environment. Here, we address the effects of dietary Trp on post-stress plasma cortisol and hypothalamic monoamines in seawater-adapted Atlantic salmon (Salmo salar), reared at densities relevant for aquaculture. Fish were given feed containing 1, 2, 3 or 4 times the Trp content in normal feed for one week. Subsequently, the fish were reintroduced to feed containing the lowest Trp level, corresponding to standard commercial feed for a number of days prior to exposure to an acute confinement stressor. Basal plasma cortisol levels were lower among non-stressed fish at 1 and 10 days post dietary Trp supplementation. By comparison, stressed fish displayed stimulatory post-stress plasma cortisol responses at 1 and 2 days after the Trp regimen was terminated. However, a reversed pattern was observed among these fish at 10 days after Trp treatment. The overall effects of dietary Trp were more pronounced in dopamine (DA) neurochemistry compared to 5-HT in the hypothalamus. The results demonstrate both short-and long-term effects of elevated dietary Trp on the neuroendocrine stress response. These findings suggest that hypothalamic DA may be more involved than 5-HT in the stress reducing effects of Trp in seawater-adapted Atlantic salmon, reared at densities relevant for aquaculture.
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3. |
- Marshall, Paul R., et al.
(författare)
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DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory
- 2024
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Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 44:15
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Tidskriftsartikel (refereegranskat)abstract
- The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here, we report that G-quadruplex DNA (G4-DNA) accumulates in neurons, in an experience-dependent manner, and that this is required for the transient silencing and activation of genes that are critically involved in learning and memory in male C57/BL6 mice. In addition, site-specific resolution of G4-DNA by dCas9-mediated deposition of the helicase DHX36 impairs fear extinction memory. Dynamic DNA structure states therefore represent a key molecular mechanism underlying memory consolidation. One-Sentence Summary: G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.
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4. |
- Schjolden, Joachim, et al.
(författare)
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Aggression in rainbow trout is inhibited by both MR and GR antagonists
- 2009
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Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 98:5, s. 625-630
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The present study has investigated the effect of exogenous cortisol on aggression in juvenile rainbow trout, along with the involvement of mineralocorticoid (MR) and glucocorticoid receptors (GR) mediating the effects of cortisol. Fish were fed pellets supplemented with cortisol, the GR antagonist mifepristone (RU486) in combination with cortisol, the MR antagonist spironolactone (SA) in combination with cortisol or both antagonists in combination with cortisol. Aggressive behaviour was then assessed I h subsequent to feeding. Our results showed that the attack latency was increased by exogenous cortisol, an effect that was not abolished by the antagonists. The intensity of aggression was not changed by exogenous cortisol. However, the intensity of aggression was significantly reduced by both antagonists. These results are discussed with regard to cortisol affecting aggressive behaviour through genomic and non-genomic pathways. Our results have demonstrated the involvement of both MR and GR in regulating behavioural responses during social interactions in teleost fish. The intensity of aggression seen in control and cortisol treated fish is probably mediated by the basal levels of cortisol through the intracellular MRs and GRs. We conclude that the initiative to engage in social confrontations is mediated through a non-genomic pathway, which could involve extracellular corticoid receptors. Further, the majority of arguments lean towards the MR and GR antagonists blocking the effect of cortisol on aggressive intensity through intracellular receptors. If this is the case, then it is probable that these two aspects of aggressive behaviour are based on different neuronal mechanisms.
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5. |
- Tedesco-Silva, Helio, et al.
(författare)
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Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants : An Analysis From the Randomized TRANSFORM Study
- 2019
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 103:9, s. 1953-1963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail.METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids.RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA.CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.
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