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https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#1
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29329285/a-direct-interaction-of-cholesterol-with-the-dopamine-transporter-prevents-its-out-to-inward-transition
#2
Talia Zeppelin, Lucy Kate Ladefoged, Steffen Sinning, Xavier Periole, Birgit Schiøtt
Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation...
January 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29329256/personalized-antidepressant-selection-and-pathway-to-novel-treatments-clinical-utility-of-targeting-inflammation
#3
REVIEW
Manish K Jha, Madhukar H Trivedi
Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments...
January 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29324833/evidence-for-pmat-and-oct-like-biogenic-amine-transporters-in-a-probiotic-strain-of-lactobacillus-implications-for-interkingdom-communication-within-the-microbiota-gut-brain-axis
#4
Mark Lyte, David R Brown
The ability of prokaryotic microbes to produce and respond to neurochemicals that are more often associated with eukaryotic systems is increasingly recognized through the concept of microbial endocrinology. Most studies have described the phenomena of neurochemical production by bacteria, but there remains an incomplete understanding of the mechanisms by which microbe- or host-derived neuroactive substances can be recognized by bacteria. Based on the evolutionary origins of eukaryotic solute carrier transporters, we hypothesized that bacteria may possess an analogous uptake function for neuroactive biogenic amines...
2018: PloS One
https://www.readbyqxmd.com/read/29324067/mao-inhibitors-and-their-wider-applications-a-patent-review
#5
Simone Carradori, Daniela Secci, Jacques P Petzer
Monoamine oxidase (MAO) inhibitors, after the initial "golden age", are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism. Areas covered: In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold...
January 11, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29322377/s-ketamine-current-trends-in-emergency-and-intensive-care-medicine
#6
REVIEW
Helmut Trimmel, Raimund Helbok, Thomas Staudinger, Wolfgang Jaksch, Brigitte Messerer, Herbert Schöchl, Rudolf Likar
S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L‑type calcium chanels have also been described...
January 10, 2018: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/29321989/antidepressant-like-effects-of-gan-mai-dazao-tang-via-monoamine-regulatory-pathways-on-forced-swimming-test-in-rats
#7
Hsiang-Ling Huang, Swee-Ling Lim, Kuan-Hung Lu, Lee-Yan Sheen
Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (, gān mài dà zǎo tang) is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice), Triticum aestivum L. (wheat) and Zizphus jujuba Mill. (jujube)...
January 2018: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29320717/imitation-of-phase-i-metabolism-reactions-of-mao-a-inhibitors-by-titanium-dioxide-photocatalysis
#8
Maciej Gawlik, Jakub Trawiński, Robert Skibiński
The imitation of phase I metabolism of moclobemide and toloxatone, two monoamine oxidase type A (MAO-A) inhibitors, was performed with the use of titanium dioxide photocatalytic process. Ultra high pressure liquid chromatography system coupled with an accurate hybrid ESI-Q-TOF mass spectrometer was used for the evaluation of metabolic profiles, structural elucidation of the identified transformation products and quantitative analysis of the process. Based on high resolution MS and MS/MS data, eleven transformation products were characterized in photocatalytic experiments for moclobemide and seven products for toloxatone...
January 8, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29317067/nigral-depigmentation-reflects-monoamine-exhaustion-as-initial-step-to-parkinson-s-disease
#9
Thomas Müller, Willi Kohlhepp
This hypothesis discusses exposure and response to various stressors as cause for chronic neurodegeneration. Predisposing genetic and environmental factors in conjunction with exposure to exogenous and endogenous toxins cause stress, which consumes dopamine and related biogenic amines. To compensate monoamine exhaustion, conversion of endogenous levodopa to dopamine by tyrosine hydroxylase is up regulated. Concomitantly, tyrosine mediated levodopa degradation to dopaquinone is reduced. Dopaquinone is the essential precursor of neuromelanin...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316677/design-synthesis-and-biological-evaluation-of-novel-n-pyridyl-hydrazone-derivatives-as-potential-monoamine-oxidase-mao-inhibitors
#10
Gülhan Turan-Zitouni, Weiam Hussein, Begüm Nurpelin Sağlık, Aouatef Tabbi, Büşra Korkut
A new series of N-pyridyl-hydrazone derivatives was synthesized by using a simple and efficient method. The final compounds obtained were screened for their inhibitory potency against monoamine oxidase (MAO) A and B. The newly synthesized compounds 2a-2n specifically inhibited monoamine oxidases, displaying notably low IC50 values. Compounds 2i and 2j, with a CF₃ and OH group on the 4-position of the phenyl ring, respectively, showed considerable MAO-A and MAO-B inhibitory activities. Compounds 2k, 2l and 2n, with N-methylpyrrole, furan and pyridine moieties instead of the phenyl ring, were the most powerful and specific inhibitors of MAO-A, with IC50 values of 6...
January 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29309800/partial-reversal-of-the-effort-related-motivational-effects-of-tetrabenazine-with-the-mao-b-inhibitor-deprenyl-selegiline-implications-for-treating-motivational-dysfunctions
#11
Hector Contreras-Mora, Megan A Rowland, Samantha E Yohn, Merce Correa, John D Salamone
People with depression and Parkinsonism frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks that assess effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of monoamine oxidase (MAO) inhibitors with varying selectivity profiles to reverse the low effort bias induced by the monoamine storage inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans, and because of its selective inhibition of VMAT-2, it preferentially depletes DA at low doses...
January 5, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29306111/deuterated-18f-9-o-hexadeutero-3-fluoropropoxyl-dihydrotetrabenazine-d6-fp-dtbz-a-vesicular-monoamine-transporter-2-vmat2-imaging-agent
#12
Futao Liu, Seok Rye Choi, Zhihao Zha, Karl Ploessl, Lin Zhu, Hank F Kung
INTRODUCTION: Vesicular monoamine transporters 2 (VMAT2) in the brain serve as transporter for packaging monoamine in vesicles for normal CNS neurotransmission. Several VMAT2 imaging agents, [11C]-(+)-DTBZ, dihydrotetrabenazine and [18F]FP-(+)-DTBZ (9-O-fluoropropyl-(+)-dihydro tetrabenazine, a.k.a. [18F]AV-133), are useful for studying the changes in brain function related to monoamine transmission by in vivo imaging. Deuterated analogs have been reported targeting VMAT2 binding sites...
December 6, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29301981/controlling-of-n-alkylpolyamine-analogue-metabolism-by-selective-deuteration
#13
Sebahat Ucal, Merja R Häkkinen, Aino-Liisa Alanne, Leena Alhonen, Jouko Vepsäläinen, Tuomo A Keinänen, Mervi T Hyvönen
Replacing protium with deuterium is an efficient method to modulate drug metabolism. N -alkylated polyamine analogues are polyamine antimetabolites with proven anticancer efficacy. We have characterized earlier the preferred metabolic routes of N1,N12 -diethylspermine (DESpm), N1 -benzyl- N12 -ethylspermine (BnEtSpm) and N1,N12 -dibenzylspermine (DBSpm) by human recombinant spermine oxidase (SMOX) and acetylpolyamine oxidase (APAO). Here we studied the above analogues, their variably deuterated counterparts and their metabolites as substrates and inhibitors of APAO, SMOX, semicarbazide-sensitive amine oxidase (SSAO), diamine oxidase (DAO) and monoamine oxidases...
January 4, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29301680/moderate-intensity-exercise-induced-catecholamine-release-in-the-preoptic-area-and-anterior-hypothalamus-in-rats-is-enhanced-in-a-warm-environment
#14
Xinyan Zheng, Satomi Takatsu, Ryo Ishikawa, Hiroshi Hasegawa
Thermoeffector responses and core body temperature (Tcore) homeostasis during exercise are affected by both ambient temperature and exercise intensity. We have previously reported that Tcore, heat loss responses, and catecholamine release in the preoptic area and anterior hypothalamus (PO/AH) increased during incremental treadmill running. However, no previous study has examined whether changes in the thermoregulatory responses at warm ambient temperature are related to catecholamine responses during moderate intensity exercise in rats...
January 2018: Journal of Thermal Biology
https://www.readbyqxmd.com/read/29297157/astroglial-responses-to-amyloid-beta-progression-in-a-mouse-model-of-alzheimer-s-disease
#15
Malin Olsen, Ximena Aguilar, Dag Sehlin, Xiaotian T Fang, Gunnar Antoni, Anna Erlandsson, Stina Syvänen
PURPOSE: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-L-[11C]deprenyl ([11C]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i...
January 2, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29297119/expression-of-components-of-the-serotonergic-system-in-the-developing-rat-thymus
#16
N V Lifantseva, Ts O Koneeva, E E Voronezhskaya, V I Melnikova
The developing thymus of rat fetuses contains all components of the serotonergic system: receptors, enzymes of synthesis, and membrane transporters. The expression of receptors suggests the possibility of a direct influence of serotonin on thymic development. The presence of tryptophan hydroxylase (the key rate-limiting enzyme of serotonin synthesis) and aromatic l-amino acid decarboxylase indicates the ability of fetal thymic cells to synthesize serotonin. It was shown that the cells of a developing thymus can actively uptake extracellular monoamines...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29290056/presynaptic-serotonin-5-ht1b-d-receptor-mediated-inhibition-of-glycinergic-transmission-to-the-frog-spinal-motoneurons
#17
N I Kalinina, Aleksey V Zaitsev, N P Vesselkin
Endogenous monoamine 5-hydroxytryptamine (5-HT, serotonin) is a phylogenetically ancient neurotransmitter present in vertebrates. The functions of 5-HT in central nervous system are intensively studied; however, the presynaptic effects of 5-HT in frog spinal motoneurons are practically unexplored. We have previously shown that 5-HT decreases the frequency of glycinergic miniature inhibitory postsynaptic potentials (mIPSPs), but does not affect the frequency of GABAergic mIPSPs and increases the frequency of glutamatergic postsynaptic potentials...
December 30, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29288796/dha-mitigates-autistic-behaviors-accompanied-by-dopaminergic-change-in-a-gene-prenatal-stress-mouse-model
#18
Fumihiro Matsui, Patrick Hecht, Kanji Yoshimoto, Yoshihisa Watanabe, Masafumi Morimoto, Kevin Fritsche, Matthew Will, David Beversdorf
Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction, social communication, and repetitive and stereotyped behaviors. Recent work has begun to explore gene x environmental interactions in the etiology of ASD. We previously reported that prenatal stress exposure in stress-susceptible heterozygous serotonin transporter (SERT) KO pregnant dams in a mouse model resulted in autism-like behavior in the offspring (SERT/S mice). The association between prenatal stress and ASD appears to be affected by maternal SERT genotype in clinical populations as well...
December 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/29288046/taar5-receptor-agonist-affects-sensory-gating-in-rats
#19
Aleksander A Aleksandrov, Elena S Dmitrieva, Anna B Volnova, Veronika M Knyazeva, Andrey S Gerasimov, Raul R Gainetdinov
Trace amines are structurally close to classical monoamines and dysregulation in trace amines and/or their receptors might contribute to pathology of mental disorders. The study was aimed to investigate the effect of recently identified Trace Amine-Associated Receptor 5 (TAAR5) agonist 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA) on sensory gating (SG) in awake freely moving rats. SG was studied in paired-click paradigm and SG index was calculated as difference in event related potentials component N40 amplitudes to the first and second stimulus in the pair...
December 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29286588/epidemiology-and-economic-burden-of-serotonin-syndrome-with-concomitant-use-of-serotonergic-agents-a-retrospective-study-utilizing-two-large-us-claims-databases
#20
Charles T Nguyen, Lin Xie, Stephanie Alley, Robert M McCarron, Onur Baser, Zhixiao Wang
Objective: Serotonin syndrome (SS) is an adverse drug reaction occurring among patients receiving serotonergic agents (SAs), and although SAs are commonly prescribed, the epidemiology and economic burden of SS with concomitant SA use have not been comprehensively examined. The objective of this study was to investigate the prevalence, incidence, and economic burden of SS with SA use. Methods: A retrospective cohort study was conducted using Veterans Health Administration (VHA) records (identification period: October 1, 2008-September 30, 2012) and commercially insured patient records (Intercontinental Marketing Services PharMetrics Plus; identification period: January 1, 2010-December 31, 2013)...
December 28, 2017: Primary Care Companion to CNS Disorders
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