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Ken-Ichi Yamashita, Kazuyuki Kataoka, Shouichi Takeuchi, Ken-Ichi Sugiura
A facile and metal-free method for the preparation of free base meso-aminodiarylporphyrins from readily available meso-bromodiarylporphyrins is described. Simple treatment of meso-bromoporphyrins with sodium azide and sodium ascorbate in DMF affords the corresponding meso-aminoporphyrins in nearly quantitative yields. This method involves the aromatic nucleophilic substitution (SNAr) of a bromo group with an azido group and the subsequent in situ reduction of the introduced azido group by sodium ascorbate. This amination reaction can be scaled up to gram scale without any decrease of the product yield...
October 21, 2016: Journal of Organic Chemistry
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
Raquel Fonseca, Rui A Carvalho, Cristina Lemos, Ana C Sequeira, Inês R Pita, Fábio Carvalho, Carlos D Silva, Rui D S Prediger, Ivana Jarak, Rodrigo A Cunha, Carlos A Fontes Ribeiro, Attila Köfalvi, Frederico C Pereira
INTRODUCTION: We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. AIMS: Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i...
October 19, 2016: CNS Neuroscience & Therapeutics
Yimin Qiu, Dongmei Chen, Xiaojing Huang, Lina Huang, Liang Tang, Jihong Jiang, Lianhua Chen, Shitong Li
BACKGROUND: Limited surveys have assessed the performance of 5-hydroxytreptamine receptor 1A and its antagonist WAY-100635 in pharmacological manipulations targeting delirium therapies. The purpose of this paper was to assess the central pharmacological activity of WAY-100635 in a rat model of scopolamine-induced delirium and its underlying mechanism. RESULTS: A delirium rat model was established by intraperitoneal injection of scopolamine and behavioral changes evaluated through open field and elevated plus maze experiments...
October 19, 2016: BMC Neuroscience
Yong Li, Julia Hoffmann, Yang Li, Flora Stephano, Iris Bruchhaus, Christine Fink, Thomas Roeder
The monoamines octopamine (OA) and tyramine (TA) modulate numerous behaviours and physiological processes in invertebrates. Nevertheless, it is not clear whether these invertebrate counterparts of norepinephrine are important regulators of metabolic and life history traits. We show that flies (Drosophila melanogaster) lacking OA are more resistant to starvation, while their overall life span is substantially reduced compared with control flies. In addition, these animals have increased body fat deposits, reduced physical activity and a reduced metabolic resting rate...
October 19, 2016: Scientific Reports
Peter S Hasenhuetl, Michael Freissmuth, Walter Sandtner
The plasmalemmal monoamine transporters clear the extracellular space from their cognate substrates and sustain cellular monoamine stores even during neuronal activity. In some instances, however, the transporters enter a substrate-exchange mode, which results in release of intracellular substrate. Understanding what determines the switch between these two transport modes demands time-resolved measurements of intracellular (co-)substrate-binding and -release. Here, we report an electrophysiological investigation of intracellular solute-binding to the human serotonin transporter (SERT) expressed in HEK-293 cells...
October 18, 2016: Journal of Biological Chemistry
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
Evelyn Andersson, Christian Rück, Catharina Lavebratt, Erik Hedman, Martin Schalling, Nils Lindefors, Elias Eriksson, Per Carlbring, Gerhard Andersson, Tomas Furmark
[This corrects the article DOI: 10.1371/journal.pone.0079015.].
2016: PloS One
Narayan D Chaurasiya, Vedanjali Gogineni, Khaled M Elokely, Francisco León, Marvin J Núñez, Michael L Klein, Larry A Walker, Stephen J Cutler, Babu L Tekwani
Calea urticifolia (Asteraceae: Asteroideae) has long been used as a traditional medicine in El Salvador to treat arthritis and fever, among other illnesses. The chloroform extract of the leaves of C. urticifolia showed potent inhibition of recombinant human monoamine oxidases (MAO-A and -B). Further bioassay-guided fractionation led to the isolation of a flavonoid, acacetin, as the most prominent MAO inhibitory constituent, with IC50 values of 121 and 49 nM for MAO-A and -B, respectively. The potency of MAO inhibition by acacetin was >5-fold higher for MAO-A (0...
October 18, 2016: Journal of Natural Products
Ganiyu Oboh, Omodesola O Ogunruku, Sunday I Oyeleye, Tosin A Olasehinde, Ayokunle O Ademosun, Aline Augusti Boligon
This study investigated the inhibitory effects of phenolic-rich extracts from Clerodendrum volubile leaves on cholinergic [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoaminergic [monoamine oxidase (MAO)] enzymes' activities and pro-oxidants [Fe(2+) and quinolinic acid-(QA)] induced lipid peroxidation in rats brain homogenates in vitro. Free phenolic extracts (FPE) and bound phenolic extracts (BPE) were obtained via solvent extraction, and the total phenol and flavonoid contents were evaluated...
October 18, 2016: Journal of Dietary Supplements
Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Eunsoo Won, Sunyoung Choi, June Kang, Min-Soo Lee, Byung-Joo Ham
BACKGROUND: Orbitofrontal cortex alterations have been suggested to underlie the impaired mood regulation in depression. MAOA-uVNTR (monoamine oxidase A-upstream variable number of tandem repeats) polymorphism has been reported to be associated with major depressive disorder by various studies. The influence of MAOA-uVNTR genotype on function and structure of the orbitofrontal cortex has previously been reported. In this study, we investigated the difference in orbitofrontal cortex thickness between medication-naïve female patients with major depressive disorder and healthy controls, and the influence of MAOA-uVNTR genotype on orbitofrontal cortex thickness in depression...
2016: Annals of General Psychiatry
John E Cebak, Indrapal N Singh, Rachel L Hill, Juan Wang, Edward D Hall
Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or the propagation of lipid peroxidation (LP). A more recently explored approach involves scavenging the terminal LP breakdown products that are highly reactive and neurotoxic carbonyl compounds 4-hydroxynonenal (4-HNE) and acrolein to prevent their covalent modification and rendering of cellular proteins non-functional leading to loss of ionic homeostasis, mitochondrial failure, and subsequent neuronal death...
October 18, 2016: Journal of Neurotrauma
Michael Saul, Petra Majdak, Samuel Perez, Matthew Reilly, Theodore Garland, Justin S Rhodes
Though exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days...
October 17, 2016: Genes, Brain, and Behavior
Anna Ngo, Ann Koay, Christian Pecquet, Carmen C Diaconu, Yasmine Ould-Amer, Qiwei Huang, Congbao Kang, Anders Poulsen, May Ann Lee, David Jenkins, Andrew Shiau, Stefan N Constantinescu, Meng Ling Choo
BACKGROUND: Rather than a Janus Kinase 2 inhibitor (ruxolitinib), a specific thrombopoietin receptor (TpoR) inhibitor would be more specific for the treatment of myeloproliferative neoplasms due to TpoR mutations. OBJECTIVE: A cell-based phenotypic approach to identify specific TpoR inhibitors was implemented and a library of 505,483 small molecules was screened for inhibitory effects on cells transformed by TpoR mutants. RESULTS: Among the identified hits are two analogs of 3-(4-piperidinyl) indole...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Juliana Maria de Mello Andrade, Natasha Maurmann, Patricia Pranke, Izabel Cristina Casanova Turatti, Norberto Peporine Lopes, Amélia T Henriques
OBJECTIVES: The hexane (HEX) and dichloromethane (DCM) fractions from Blechnum binervatum, Blechnum brasiliense and Blechnum occidentale were studied about phytochemicals and biological properties using multitarget approach. METHODS: The chemical composition was performed by gas chromatography coupled with mass spectrometry detector (GC-MS) analysis. Antioxidant capacity was evaluated against free radicals and on lipid peroxidation. Monoamine oxidases (MAO) and cholinesterases enzymatic modulation, as well as effects on rat and human cells, were assessed...
October 17, 2016: Journal of Pharmacy and Pharmacology
Jacques Joubert, Germaine B Foka, Benjamin P Repsold, Douglas W Oliver, Erika Kapp, Sarel F Malan
A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC50: 0...
September 15, 2016: European Journal of Medicinal Chemistry
Hsiu-Chiung Lee, Wei-Che Chiu, Tsu-Nai Wang, Yin-To Liao, I-Chia Chien, Yena Lee, Roger S McIntyre, Pau-Chung Chen, Vincent Chin-Hung Chen
BACKGROUND: Experimental evidence indicates that serotonin is associated with both proliferative and pro-carcinogenic effects on colorectal tumors. The present study aims to investigate the associations between antidepressant use and colorectal cancer in an epidemiological sample. METHODS: We conducted a population-based case-control study utilizing Taiwan's National Health Insurance Research Database (NHIRD). We identified 49,342 cases with colorectal cancer and 240,985 controls between 1997 and 2008...
October 1, 2016: Journal of Affective Disorders
Harald H Sitte, Christian Pifl, Ali H Rajput, Heide Hörtnagl, Junchao Tong, George K Lloyd, Stephen J Kish, Oleh Hornykiewicz
In the human brain, the claustrum is a small subcortical telencephalic nucleus, situated between the insular cortex and the putamen. A plethora of neuroanatomical studies have shown the existence of dense, widespread, bidirectional and bilateral monosynaptic interconnections between the claustrum and most cortical areas. A rapidly growing body of experimental evidence points to the integrative role of claustrum in complex brain functions, from motor to cognitive. Here, we examined for the first time, the behaviour of the classical monoamine neurotransmitters dopamine, noradrenaline and serotonin in the claustrum of the normal autopsied human brain and of patients who died with idiopathic Parkinson's disease (PD)...
October 14, 2016: European Journal of Neuroscience
Susanne A Bengesser, Eva Z Reininghaus, Nina Lackner, Armin Birner, Frederike T Fellendorf, Martina Platzer, Nora Kainzbauer, Bernhard Tropper, Christa Hörmanseder, Robert Queissner, Hans-Peter Kapfhammer, Sandra J Wallner-Liebmann, Robert Fuchs, Erwin Petek, Christian Windpassinger, Mario Schnalzenberger, Bernd Reininghaus, Bernd Evert, Andreas Waha
OBJECTIVES: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. METHODS: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing...
October 14, 2016: World Journal of Biological Psychiatry
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