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https://www.readbyqxmd.com/read/28220990/oxidative-stress-serotonergic-changes-and-decreased-ultrasonic-vocalizations-in-a-mouse-model-of-smith-lemli-opitz-syndrome
#1
Navila F Sharif, Zeljka Korade, Ned A Porter, Harrison Fiona E
Smith Lemli Opitz syndrome is an inherited monogenic disorder in which mutations to the Dhcr7 gene lead to deficits in cholesterol synthesis. As a result, many patients suffer from gross physiological and neurological deficits. The purpose of this study was to identify a potential abnormal behavioral phenotype in a compound mutant mouse model for Smith Lemli Opitz disease (Dhcr7(Δ3)(-5/)(T93M) ) to further validate the model, and to provide potential targets for future therapeutic interventions. We also sought to identify some of the underlying changes in brain function that may be responsible for behavioral differences among groups...
February 21, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28220701/deconstructed-analogs-of-bupropion-reveal-structural-requirements-for-transporter-inhibition-versus-substrate-induced-neurotransmitter-release
#2
Abdelrahman R Shalabi, Donna Walther, Michael H Baumann, Richard A Glennon
Bupropion (1), an α-aminophenone uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET), is a widely prescribed antidepressant and smoking cessation aid. Cathinone (2), a structurally simpler α-aminophenone, is a substrate-type releasing agent at the same transporters and a recognized drug of abuse. Our goal was to identify the structural features of α-aminophenones that govern the mechanistic transition from uptake inhibition to substrate-induced release. Deconstructed analogs of 1 were synthesized and compared for their ability to interact with DAT, NET, and the serotonin transporter (SERT) using in vitro assay methods...
February 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28220069/effects-of-selective-serotonin-reuptake-inhibitors-on-interregional-relation-of-serotonin-transporter-availability-in-major-depression
#3
Gregory M James, Pia Baldinger-Melich, Cecile Philippe, Georg S Kranz, Thomas Vanicek, Andreas Hahn, Gregor Gryglewski, Marius Hienert, Marie Spies, Tatjana Traub-Weidinger, Markus Mitterhauser, Wolfgang Wadsak, Marcus Hacker, Siegfried Kasper, Rupert Lanzenberger
Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI's main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BPND)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28209599/role-of-shp2-protein-tyrosine-phosphatase-in-sert-inhibition-by-enteropathogenic-e-coli-epec
#4
Megha Singhal, Christopher Manzella, Vinay Soni, Waddah A Alrefai, Seema Saksena, Gail A Hecht, Pradeep K Dudeja, Ravinder K Gill
Enteropathogenic E. coli (EPEC), one of the diarrheagenic E. coli pathotypes, is among the most important food-borne pathogens infecting children worldwide. Inhibition of serotonin transporter (SERT), that regulates extracellular availability of serotonin (5-HT), has been previously implicated in EPEC-associated diarrhea. EPEC was shown to inhibit SERT via activation of protein tyrosine phosphatases (PTPase), albeit the specific PTPase involved is not known. Current studies aimed to identify EPEC activated PTPase and its role in SERT inhibition...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28203264/a-pilot-study-exploring-the-association-of-morphological-changes-with-5-httlpr-polymorphism-in-ocd-patients
#5
Shinichi Honda, Tomohiro Nakao, Hiroshi Mitsuyasu, Kayo Okada, Leo Gotoh, Mayumi Tomita, Hirokuni Sanematsu, Keitaro Murayama, Keisuke Ikari, Masumi Kuwano, Takashi Yoshiura, Hiroaki Kawasaki, Shigenobu Kanba
BACKGROUND: Clinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables. METHODS: We carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs)...
2017: Annals of General Psychiatry
https://www.readbyqxmd.com/read/28203149/gene-gene-environment-interactions-of-serotonin-transporter-monoamine-oxidase-a-and-childhood-maltreatment-predict-aggressive-behavior-in-chinese-adolescents
#6
Yun Zhang, Qing-Sen Ming, Jin-Yao Yi, Xiang Wang, Qiao-Lian Chai, Shu-Qiao Yao
Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28195567/bdnf-val66met-association-with-serotonin-transporter-binding-in-healthy-humans
#7
P M Fisher, B Ozenne, C Svarer, D Adamsen, S Lehel, W F C Baaré, P S Jensen, G M Knudsen
The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [(11)C]DASB positron emission tomography (PET) in a comparatively large cohort of 144 healthy individuals...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28194630/source-based-morphometry-multivariate-approach-to-analyze-123-i-fp-cit-spect-imaging
#8
Enrico Premi, V D Calhoun, V Garibotto, R Turrone, A Alberici, E Cottini, A Pilotto, S Gazzina, M Magoni, B Paghera, B Borroni, A Padovani
PURPOSE: [(123)I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [(123)I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks...
February 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28192169/the-serotonin-transporter-polymorphism-5-httlpr-and-coping-strategies-influence-successful-emotion-regulation-in-an-acute-stress-situation-physiological-evidence
#9
Thomas Plieger, Martin Melchers, Annabel Vetterlein, Janina Görtz, Sarah Kuhn, Melissa Ruppel, Martin Reuter
INTRODUCTION: Emotion regulation is an important everyday-life skill to reduce harm and stress. Consequently, research shows associations between psychopathologies and emotional dysregulation. The serotonin transporter polymorphism (5-HTTLPR) has repeatedly been associated to phenotypes and syndromes related to emotional dysregulation. However, there is no study showing any direct effects of 5-HTTLPR genotype and emotion regulation. Hence, the aim of the present study was to draw a link between 5-HTTLPR to emotion regulation...
February 9, 2017: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/28185878/chronic-mild-stress-augments-mptp-induced-neurotoxicity-in-a-murine-model-of-parkinson-s-disease
#10
Udaiyappan Janakiraman, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Chinnasamy Dhanalakshmi, Musthafa Mohamed Essa, Byoung-Joon Song, Gilles J Guillemin
Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice...
February 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28182708/comparison-of-brain-serotonin-transporter-using-i-123-adam-between-obese-and-non-obese-young-adults-without-an-eating-disorder
#11
Chih-Hsing Wu, Chin-Sung Chang, Yen Kuang Yang, Lie-Hang Shen, Wei-Jen Yao
Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46...
2017: PloS One
https://www.readbyqxmd.com/read/28176009/dopamine-and-serotonin-modulation-of-motor-and-non-motor-functions-of-the-non-human-primate-striato-pallidal-circuits-in-normal-and-pathological-states
#12
REVIEW
Véronique Sgambato-Faure, Léon Tremblay
Thanks to the non-human primate (NHP), we have shown that the pharmacological disturbance of the anterior striatum or of external globus pallidus triggers a set of motivation and movement disorders, depending on the functional subterritory involved. One can, therefore, assume that the aberrant activity of the different subterritories of basal ganglia (BG) could lead to different behavioral disorders in neuropsychiatric disorders as Tourette's syndrome and Parkinson's disease. We are now addressing in the NHP the impact of modulating dopamine or serotonin within the BG on behavioral disorders...
February 7, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28163672/targeting-neuroblastoma-cell-surface-proteins-recommendations-for-homology-modeling-of-hnet-alk-and-trkb
#13
Yazan Haddad, Zbyněk Heger, Vojtech Adam
Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28127108/the-development-of-screening-methods-to-identify-drugs-to-limit-er-stress-using-wild-type-and-mutant-serotonin-transporter
#14
Kazusa Katarao, Seiya Murakawa, Masaya Asano, Naoto Usuki, Hikaru Yamamoto, Toshihiko Shirafuji, Shigeru Tanaka, Izumi Hide, Norio Sakai
The function of the serotonin transporter (SERT) is regulated by its membrane trafficking. Previously, we showed that the C-terminus-deleted mutant of SERT (SERTΔCT) exhibited an aberrant membrane trafficking and subsequent retention at the endoplasmic reticulum (ER). In addition, we found that proteasome inhibitor-induced ER stress resulted in the impairment of SERT membrane trafficking and retention of SERT at the ER, an impairment very similar to that of SERTΔCT. Based on the result that the chemical chaperone 4-phnylbutulic acid (4-PBA), which relieves ER stress, accelerated the membrane trafficking and upregulated SERT activity, we hypothesized that drugs that facilitate the membrane trafficking of SERT would have potential therapeutic effects on an ER stress-related disease...
December 28, 2016: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/28119137/simple-and-rapid-quantification-of-serotonin-transporter-binding-using-11-c-dasb-bolus-plus-constant-infusion
#15
G Gryglewski, L Rischka, C Philippe, A Hahn, G M James, E Klebermass, M Hienert, L Silberbauer, T Vanicek, A Kautzky, N Berroterán-Infante, L Nics, T Traub-Weidinger, M Mitterhauser, W Wadsak, M Hacker, S Kasper, R Lanzenberger
INTRODUCTION: In-vivo quantification of serotonin transporters (SERT) in human brain has been a mainstay of molecular imaging in the field of neuropsychiatric disorders and helped to explore the underpinnings of several medical conditions, therapeutic and environmental influences. The emergence of PET/MR hybrid systems and the heterogeneity of SERT binding call for the development of efficient methods making the investigation of larger or vulnerable populations with limited scanner time and simultaneous changes in molecular and functional measures possible...
January 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/28109119/serotonin-transporter-protects-the-placental-cells-against-apoptosis-in-caspase-3-independent-pathway
#16
Coedy Hadden, Tariq Fahmi, Anthonya Cooper, Alena V Savenka, Vladimir V Lupashin, Drucilla J Roberts, Luc Maroteaux, Sylvie Hauguel-de Mouzon, Fusun Kilic
Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28104804/the-n-terminus-specifies-the-switch-between-transport-modes-of-the-human-serotonin-transporter
#17
Carina Kern, Fatma Asli Erdem, Ali El-Kasaby, Walter Sandtner, Michael Freissmuth, Sonja Sucic
The serotonin transporter (SERT) and other monoamine transporters operate in either a forward transport mode, where the transporter undergoes a full transport cycle, or an exchange mode, where the transporter seesaws through half-cycles. Amphetamines trigger the exchange-mode leading to substrate efflux. This efflux was proposed to rely on the N-terminus, which was suggested to adopt different conformations in the inward-, outward-facing and amphetamine-bound states. This prediction was verified by tryptic digestion of SERT-expressing membranes: in the absence of Na+, the N-terminus was rapidly digested...
January 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28103426/analytical-characterization-and-pharmacological-evaluation-of-the-new-psychoactive-substance-4-fluoromethylphenidate-4%C3%A2-f-mph-and-differentiation-between-the-%C3%A2-threo-and-%C3%A2-erythro-diastereomers
#18
Gavin McLaughlin, Noreen Morris, Pierce V Kavanagh, John D Power, Geraldine Dowling, Brendan Twamley, John O'Brien, Gary Hessman, Brian Murphy, Donna Walther, John S Partilla, Michael H Baumann, Simon D Brandt
Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®, MPH) has long been acknowledged, but the appearance of MPH analogs in the form of 'research chemicals' has only emerged in more recent years. 4-Fluoromethylphenidate (4 F-MPH) is one of these recent examples and this study presents the identification and analytical characterization of two powdered 4 F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4 F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4 F-MPH...
January 19, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28102547/commentary-targeting-nmda-receptor-and-serotonin-transporter-for-the-treatment-of-comorbid-alcohol-dependence-and-depression
#19
Youssef Sari
No abstract text is available yet for this article.
February 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28102201/direct-pip2-binding-mediates-stable-oligomer-formation-of-the-serotonin-transporter
#20
Andreas Anderluh, Tina Hofmaier, Enrico Klotzsch, Oliver Kudlacek, Thomas Stockner, Harald H Sitte, Gerhard J Schütz
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization...
January 19, 2017: Nature Communications
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