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- Parrado-Fernandez, C, et al.
(author)
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Corrigendum
- 2019
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In: Journal of cellular and molecular medicine. - : Wiley. - 1582-4934 .- 1582-1838. ; 23:6, s. 4489-4489
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Journal article (other academic/artistic)
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- Rodriguez-Rodriguez, P, et al.
(author)
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Corrigendum
- 2018
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 141:5, s. e43-
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Journal article (peer-reviewed)
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- Tajeddinn, W., et al.
(author)
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5-HT1B and other related serotonergic proteins are altered in APPswe mutation
- 2015
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 594, s. 137-143
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Journal article (peer-reviewed)abstract
- Serotonergic dysfunction is implicated in Alzheimer's disease (AD). In addition, reductions in brain of both monoamine synthesis and release have been reported. Serotonin 1B receptors (5-HT1B), along with serotonin transporter (SERT) are among the regulators of extracellular 5-HT levels. We investigated the effect of the familial AD APP (Amyloid precursor protein) K670N/M671L double mutation, APP Swedish mutation (APPswe), on the expression of 5-HT1B, SERT, MAOA, p11 and 5-HT and its metabolite 5-HIAA in SH-SY5Y human neuroblastoma cell line stably transfected with APPswe mutation. In addition, hippocampal expressions of 5-HT1B and SERT were assessed in wild type and transgenic mice expressing APPswe mutation (Tg2576) at different age groups. We found a reduction of 5-HT1B as well as SERT in both APPswe in vitro and ex vivo. P11 and 5HT were also reduced, whereas 5HT turnover and MAOA were increased. Our results indicate that APPswe induced decreased 5-HT1B expression and 5-HT release, as well as increased MAOA activity and 5-HT breakdown. Further studies to explore the detailed mechanism behind reduced 5-HT1B and SERT in AD and their clinical implications are needed.
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- Tajeddinn, W., et al.
(author)
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Pharmacological Modulations of the Serotonergic System in a Cell-Model of Familial Alzheimer's Disease
- 2016
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 53:1, s. 349-361
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Journal article (peer-reviewed)abstract
- Serotonin (5-HT) plays a central role in the integrity of different brain functions. The 5-HT homeostasis is regulated by many factors, including serotonin transporter (SERT), monoamine oxidase enzyme (MAO), and several 5-HT receptors, including the 5-HT1B. There is little knowledge how the dynamics of this system is affected by the amyloid-beta (A beta) burden of Alzheimer's disease (AD) pathology. SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of A beta pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist. Sertraline led more than 70 fold increase of 5-HT1B gene expression (p < 0.001), an increased serotonin turnover in both APPswe and control cells and reduced intracellular serotonin levels by 75% in APPswe cells but not in controls (p > 0.05). Treatment with the 5-HT1B receptor antagonist increased SERT gene-expression in control cells but not in the APPswe cells. 5-HT and 5-HT1B antagonist treatment resulted in different p11 expression patterns in APPswe cells compared to controls. Although MAOA gene expression was not changed by APPswe overexpression, adding 5-HT lead to a significant increase in MAOA gene expression in APPswe but not control cells. These findings suggest that the sensitivity of the 5-HT1B receptor and related systems is affected by APPswe overexpression, with potential relevance for pharmacologic intervention in AD. This may at least partly explain the lack of effect of SSRIs in patients with AD and depression.
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