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https://www.readbyqxmd.com/read/27909009/association-of-protein-distribution-and-gene-expression-revealed-by-pet-and-post-mortem-quantification-in-the-serotonergic-system-of-the-human-brain
#1
A Komorowski, G M James, C Philippe, G Gryglewski, A Bauer, M Hienert, M Spies, A Kautzky, T Vanicek, A Hahn, T Traub-Weidinger, D Winkler, W Wadsak, M Mitterhauser, M Hacker, S Kasper, R Lanzenberger
Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27907003/mapping-cholesterol-interaction-sites-on-serotonin-transporter-through-coarse-grained-molecular-dynamics
#2
Mariarosaria Ferraro, Matteo Masetti, Maurizio Recanatini, Andrea Cavalli, Giovanni Bottegoni
Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10...
2016: PloS One
https://www.readbyqxmd.com/read/27890559/fluoxetine-and-its-active-metabolite-norfluoxetine-disrupt-estrogen-synthesis-in-a-co-culture-model-of-the-feto-placental-unit
#3
Andrée-Anne Hudon Thibeault, Laetitia Laurent, Sung Vo Duy, Sébastien Sauvé, Patrick Caron, Chantal Guillemette, J Thomas Sanderson, Cathy Vaillancourt
The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) 2A receptor/PKC signalling pathway...
November 24, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889580/methylphenidate-modulates-dorsal-raphe-neuronal-activity-behavioral-and-neuronal-recordings-from-adolescent-rats
#4
Holly Whitt, Natasha Kharas, Nachum Dafny
Methylphenidate (MPD) is a widely prescribed psychostimulants used for the treatment of attention deficit hyperactive disorder (ADHD). Unlike the psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on the serotonin transporter, however there is evidence suggesting that the therapeutic effects of MPD may be mediated in part by alterations in serotonin transmission. This study aimed to investigate the role of the dorsal raphe (DR) nucleus, one of the major sources of serotonergic innervation in the mammalian brain, in the response to MPD exposure...
November 23, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27888722/a-pilot-study-on-predictors-of-brainstem-raphe-abnormality-in-patients-with-major-depressive-disorder
#5
Milutin Kostić, Ana Munjiza, Danilo Pesic, Amir Peljto, Ivana Novakovic, Valerija Dobricic, Dusica Lecic Tosevski, Milija Mijajlovic
BACKGROUND: Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. AIM: The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. METHODS: TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls...
November 22, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27882537/neurochemical-and-behavioral-effects-of-hypidone-hydrochloride-yl-0919-a-novel-combined-selective-serotonin-reuptake-inhibitor-and-partial-5-ht1a-agonist
#6
Li-Ming Zhang, Xiao-Yun Wang, Nan Zhao, Yu-Lu Wang, Xiao-Xu Hu, Yu-Hua Ran, Yan-Qin Liu, You-Zhi Zhang, Ri-Fang Yang, Yun-Feng Li
The purpose of the present study was to investigate the pharmacology of hypidone hydrochloride (YL-0919), a novel selective serotonin reuptake inhibitor (SSRI) and 5-hydroxytryptamine (5-HT)1A receptor agonist with high affinity for serotonin transporter (SERT) and 5-HT1A receptors. YL-0919 promoted [(35) S]GTPγ S binding at 85% of the magnitude of the full 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), suggesting that YL-0919 is a high-efficacy partial agonist of 5-HT1A receptors...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27880876/an-integrative-review-of-methylation-at-the-serotonin-transporter-gene-and-its-dialogue-with-environmental-risk-factors-psychopathology-and-5-httlpr
#7
REVIEW
H Palma-Gudiel, L Fañanás
Gene-environment (GxE) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables...
November 20, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27869229/tetratricopeptide-repeat-domain-9a-modulates-anxiety-like-behavior-in-female-mice
#8
Lee Wei Lim, Smeeta Shrestha, Yu Zuan Or, Shawn Zheng Kai Tan, Hwa Hwa Chung, Yang Sun, Chew Leng Lim, Sharafuddin Khairuddin, Thomas Lufkin, Valerie Chun Ling Lin
Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A(-/-)) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A(-/-) mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A(-/-) mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A(+/+) mice...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#9
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27865645/discovery-of-smp-304-a-novel-benzylpiperidine-derivative-with-serotonin-transporter-inhibitory-activity-and-5-ht1a-weak-partial-agonistic-activity-showing-the-antidepressant-like-effect
#10
Hidefumi Yoshinaga, Shuji Masumoto, Koji Koyama, Naoya Kinomura, Yuji Matsumoto, Taro Kato, Satoko Baba, Kenji Matsumoto, Tomoko Horisawa, Hitomi Oki, Kazuki Yabuuchi, Toru Kodo
We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate...
October 29, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27860344/combined-simulation-and-mutation-studies-to-elucidate-selectivity-of-unsubstituted-amphetamine-like-cathinones-at-the-dopamine-transporter
#11
Amir Seddik, Daan P Geerke, Thomas Stockner, Marion Holy, Oliver Kudlacek, Nicholas V Cozzi, Arnold E Ruoho, Harald H Sitte, Gerhard F Ecker
The dopamine and serotonin transporter proteins (DAT, SERT) play a vital role in behavior and mental illness. Although their substrate transport has been studied extensively, the molecular basis of their selectivity is not completely understood yet. In this study, we exploit molecular dynamics simulations combined with mutagenesis studies to shed light on the driving factors for DAT-over-SERT selectivity of a set of cathinones. Results indicate that these compounds can adopt two binding modes of which one is more favorable...
November 8, 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27856628/analysis-of-extrastriatal-123i-fp-cit-binding-contributes-to-the-differential-diagnosis-of-parkinsonian-diseases
#12
Merijn Joling, Chris Vriend, Odile A Van den Heuvel, Pieter G H M Raijmakers, Paul A Jones, Henk W Berendse, Jan Booij
: (123)I-FP-CIT SPECT can visualise and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, (123)I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. Based on previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson's disease (PD), we hypothesised that, in addition to striatal DAT binding, there would be differences in extrastriatal (123)I-FP-CIT SPECT binding to SERT between MSA, PSP and PD...
November 17, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27831486/ontogeny-of-net-expression-and-antidepressant-like-response-to-desipramine-in-wild-type-and-sert-mutant-mice
#13
Nathan C Mitchell, Melodi A Bowman, Georgianna G Gould, Wouter Koek, Lynette C Daws
Depression is a major public health concern with symptoms that are often poorly controlled by treatment with common antidepressants. This problem is compounded in juveniles and adolescents, where therapeutic options are limited to only two approved antidepressants, both selective serotonin reuptake inhibitors (SSRIs). Moreover, therapeutic benefits of SSRIs are often especially limited in certain subpopulations of depressed patients, including children and carriers of low expressing serotonin transporter (SERT) gene variants...
November 9, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27830576/structure-activity-relationships-of-synthetic-cathinones
#14
Richard A Glennon, Małgorzata Dukat
Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g., locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed "synthetic cathinones", and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27826101/serotonin-and-urocortin-1-in-the-dorsal-raphe-and-edinger-westphal-nuclei-after-early-life-stress-in-serotonin-transporter-knockout-rats
#15
Rick H A van der Doelen, Berit Robroch, Ilse A Arnoldussen, Maya Schulpen, Judith R Homberg, Tamás Kozicz
The interaction of early life stress (ELS) and the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) has been associated with increased risk to develop depression in later life. We have used the maternal separation paradigm as a model for ELS exposure in homozygous and heterozygous 5-HTT knockout rats and measured urocortin 1 (Ucn1) mRNA and/or protein levels, Ucn1 DNA methylation, as well as 5-HT innervation in the centrally projecting Edinger-Westphal (EWcp) and dorsal raphe (DR) nuclei, both implicated in the regulation of stress response...
November 5, 2016: Neuroscience
https://www.readbyqxmd.com/read/27819008/link-polymorphism-of-5-htt-promoter-region-is-associated-with-autoantibodies-in-patients-with-systemic-lupus-erythematosus
#16
Shu Li, Shuang Liu, Fan Chen, Yuqi Cheng, Ru Bai, Aiyun Lai, Zhaoping Lu, Jian Xu
Serotonin transporter linked polymorphic region (5-HTTLPR) was reported to associate with depression in systemic lupus erythematosus (SLE) patients by our team. To explore whether 5-HTTLPR plays a role in the pathogenesis of SLE, we tested 138 SLE patients and 138 age and sex matched health controls (HCs) for 5-HTTLPR by polymerase chain reaction (PCR) and agarose gel electrophoresis. Interestingly, the results suggest that the frequencies of SS genotype and S allele in SLE patients with positive anti-Sm antibody and anti-U1RNP antibody were both significantly higher than the other genotypes and alleles...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27816559/interactive-effects-of-5-httlpr-genotype-and-rearing-environment-on-affective-attitude-towards-own-infant-in-japanese-mothers
#17
Erika Sawano, Hirokazu Doi, Tomoko Nagai, Satoko Ikeda, Kauyuki Shinohara
Maternal positive attitude towards one's own infant is the cornerstone of effective parenting. Previous research has revealed an influence of both genetic and environmental factors on maternal parenting behavior, but little is known of the potential gene-environment interaction in shaping a mother's affective attitude. To address this gap, we investigated the effect of a mother's childhood rearing environment and a serotonin transporter gene polymorphism (5-HTTLPR) on affective attitude towards her infant. Our analyses found an interactive effect between rearing environment and 5-HTTLPR genotype on maternal attitude...
November 2, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27814458/test-retest-reproducibility-of-extrastriatal-binding-with-123-i-fp-cit-spect-in-healthy-male-subjects
#18
Kiwamu Matsuoka, Fumihiko Yasuno, Takayuki Shinkai, Toshiteru Miyasaka, Masato Takahashi, Kuniaki Kiuchi, Jun Kosaka, Makoto Inoue, Kimihiko Kichikawa, Masatoshi Hasegawa, Toshifumi Kishimoto
(123)I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) is used to assess striatal dopamine transporter (DAT) expression, but it can also quantify extrastriatal serotonin transporter (SERT) expressions. While FP-CIT uptake in extrastriatal regions has been quantified, no information exists on the reproducibility of the (123)I-FP-CIT specific uptake ratio (SUR) in extrastriatal regions. We investigated test-retest reproducibility of (123)I-FP-CIT binding in the striatum, the midbrain, and cortical regions in eight healthy male subjects...
December 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27807822/vortioxetine-a-review-in-cognitive-dysfunction-in-depression
#19
James E Frampton
Vortioxetine (Brintellix(®); Trintellix(®)), a generally efficacious and well tolerated antidepressant agent, is approved in the EU and USA for the treatment of major depressive disorder (MDD) in adults. The drug has a distinctive pharmacological profile (combining inhibition of the serotonin transporter with modulation of multiple serotonin receptors) and has been shown to enhance cognitive performance in various animal models and clinical trials. Across three large, placebo-controlled studies in adults with recurrent MDD, short-term treatment with vortioxetine almost always resulted in statistically significant and clinically meaningful improvements in performance on two objective measures (the Digit Symbol Substitution Test and Rey Auditory Verbal Learning Test) that together cover a broad range of cognitive domains, including executive function, attention, processing speed, learning and memory...
November 2016: Drugs
https://www.readbyqxmd.com/read/27798133/involvement-of-the-serotonin-transporter-gene-in-accurate-subcortical-speech-encoding
#20
Lenka Selinger, Katarzyna Zarnowiec, Marc Via, Immaculada C Clemente, Carles Escera
: A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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