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https://www.readbyqxmd.com/read/28438504/agomelatine-protects-against-neuronal-damage-without-preventing-epileptogenesis-in-the-kainate-model-of-temporal-lobe-epilepsy
#1
Jana Tchekalarova, Dimitrinka Atanasova, Zlatina Nenchovska, Milena Atanasova, Lidia Kortenska, Rumyana Gesheva, Nikolai Lazarov
Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE)...
April 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28434742/endocrine-and-metabolic-changes-in-transition-dairy-cows-are-affected-by-prepartum-infusions-of-a-serotonin-precursor
#2
Lorenzo E Hernández-Castellano, Laura L Hernandez, Helga Sauerwein, Rupert M Bruckmaier
Serotonin (5-HT) has been shown to be involved in calcium homeostasis, modulating calcium concentration in blood. In addition, 5-HT participates in a variety of metabolic pathways, mainly through the modulation of glucose and lipid metabolism. The hypothesis of the present study was that the prepartum administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, would affect endocrine systems related to calcium homeostasis, and interact with other endocrine and metabolic pathways during the transition period...
April 20, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28433458/linking-the-biological-underpinnings-of-depression-role-of-mitochondria-interactions-with-melatonin-inflammation-sirtuins-tryptophan-catabolites-dna-repair-and-oxidative-and-nitrosative-stress-with-consequences-for-classification-and-cognition
#3
REVIEW
George Anderson
The pathophysiological underpinnings of neuroprogressive processes in recurrent major depressive disorder (rMDD) are reviewed. A wide array of biochemical processes underlie MDD presentations and their shift to a recurrent, neuroprogressive course, including: increased immune-inflammation, tryptophan catabolites (TRYCATs), mitochondrial dysfunction, aryl hydrocarbonn receptor activation, and oxidative and nitrosative stress (O&NS), as well as decreased sirtuins and melatonergic pathway activity. These biochemical changes may have their roots in central, systemic and/or peripheral sites, including in the gut, as well as in developmental processes, such as prenatal stressors and breastfeeding consequences...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#4
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28378373/chloroplast-overexpression-of-rice-caffeic-acid-o-methyltransferase-increases-melatonin-production-in-chloroplasts-via-the-5-methoxytryptamine-pathway-in-transgenic-rice-plants
#5
Geun-Hee Choi, Hyoung Yool Lee, Kyoungwhan Back
Recent analyses of the enzymatic features of various melatonin biosynthetic genes from bacteria, animals, and plants have led to the hypothesis that melatonin could be synthesized via the 5-methoxytryptamine (5-MT) pathway. 5-MT is known to be synthesized in vitro from serotonin by the enzymatic action of O-methyltransferases, including N-acetylserotonin methyltransferase (ASMT) and caffeic acid O-methyltransferase (COMT), leading to melatonin synthesis by the subsequent enzymatic reaction with serotonin N-acetyltransferase (SNAT)...
April 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28368307/trpv4-stimulation-induced-melatonin-secretion-by-increasing-arylalkymine-n-acetyltransferase-aanat-protein-level
#6
Hanan Awad Alkozi, Maria J Perez de Lara, Juan Sánchez-Naves, Jesús Pintor
Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine N-acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied...
April 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28282869/inhibition-of-vegf-induced-vegfr-2-activation-and-huvec-migration-by-melatonin-and-other-bioactive-indolic-compounds
#7
Ana B Cerezo, Ruth Hornedo-Ortega, M Antonia Álvarez-Fernández, Ana M Troncoso, M Carmen García-Parrilla
Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA...
March 8, 2017: Nutrients
https://www.readbyqxmd.com/read/28228148/the-effect-of-melatonin-on-depressive-symptoms-anxiety-circadian-and-sleep-disturbances-in-patients-after-acute-coronary-syndrome-medacis-study-protocol-for-a-randomized-controlled-trial
#8
Michael Tvilling Madsen, Anders Isbrand, Ulla Overgaard Andersen, Lars Juel Andersen, Mustafa Taskiran, Erik Simonsen, Ismail Gögenur
BACKGROUND: Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS...
February 23, 2017: Trials
https://www.readbyqxmd.com/read/28118532/regulating-the-balance-between-the-kynurenine-and-serotonin-pathways-of-tryptophan-metabolism
#9
Yang Li, Nan Hu, Dan Yang, Gregory Oxenkrug, Qing Yang
Tryptophan is metabolized along the kynurenine and serotonin pathways, resulting in formation of kynurenine metabolites, neuroactive serotonin and melatonin. Each pathway is critical for maintaining healthy homeostasis. However, the two pathways are extremely unequal in their ability to degrade tryptophan, and little is known about the mechanisms maintaining the balance between them. Here, we demonstrated that in PC12 cells, a change of expression of key genes of one pathway resulted in a change of expression of key genes of the other...
January 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28118490/overexpression-of-rice-serotonin-n-acetyltransferase-1-in-transgenic-rice-plants-confers-resistance-to-cadmium-and-senescence-and-increases-grain-yield
#10
Kyungjin Lee, Kyoungwhan Back
While ectopic overexpression of serotonin N-acetyltransferase (SNAT) in plants has been accomplished using animal SNAT genes, ectopic overexpression of plant SNAT genes in plants has not been investigated. Because the plant SNAT protein differs from that of animals in its subcellular localization and enzyme kinetics, its ectopic overexpression in plants would be expected to give outcomes distinct from those observed from overexpression of animal SNAT genes in transgenic plants. Consistent with our expectations, we found that transgenic rice plants overexpressing rice (Oryza sativa) SNAT1 (OsSNAT1) did not show enhanced seedling growth like that observed in ovine SNAT-overexpressing transgenic rice plants, although both types of plants exhibited increased melatonin levels...
January 24, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28110215/neuroprotective-action-of-n-acetyl-serotonin-in-oxidative-stress-induced-apoptosis-through-the-activation-of-both-trkb-creb-bdnf-pathway-and-akt-nrf2-antioxidant-enzyme-in-neuronal-cells
#11
Jae-Myung Yoo, Bo Dam Lee, Dai-Eun Sok, Jin Yuel Ma, Mee Ree Kim
N-acetyl serotonin (NAS) as a melatonin precursor has neuroprotective actions. Nonetheless, it is not clarified how NAS protects neuronal cells against oxidative stress. Recently, we have reported that N-palmitoyl serotonins possessed properties of antioxidants and neuroprotection. Based on those, we hypothesized that NAS, a N-acyl serotonin, may have similar actions in oxidative stress-induced neuronal cells, and examined the effects of NAS based on in vitro and in vivo tests. NAS dose-dependently inhibited oxidative stress-induced cell death in HT-22 cells...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28012610/secondary-to-excessive-melatonin-synthesis-the-consumption-of-tryptophan-from-outside-the-blood-brain-barrier-and-melatonin-over-signaling-in-the-pars-tuberalis-may-be-central-to-the-pathophysiology-of-winter-depression
#12
José Carlos Pereira, Márcia Pradella Hallinan, Rosana Cardoso Alves
Seasonal affective disorder is defined as recurrent episodes of major depression, mania, or hypomania with seasonal onset and remission. In this class of mood disturbances, a unipolar major depressive disorder known as winter depression is common in populations living in northern latitudes far from the equator. Winter depression repeatedly occurs in the autumn or winter and remits in the spring or summer, and its etiopathogenesis is currently unknown. However, one can surmise that excessive melatonin production during the reduced duration of daily sunlight in the autumn and winter plays a role in its pathophysiology...
January 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28006716/biomolecular-aspects-of-depression-a-retrospective-analysis
#13
Brandon N Peacock, David J Scheiderer, Gottfried H Kellermann
OBJECTIVE: The effects of psychological stress, oxidative stress, and chronic low grade inflammation on the neuro-immune connection have been implicated in the pathogenesis of depression. Thus, in the recent past, there has been a growing effort in determining the mechanism of this pathogenesis. While attempting to map out, this mechanism researchers and clinicians have searched for clinically relevant biomarkers for use in the diagnosis and for the assessment of those suffering from depression...
February 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/27999295/special-issue-molecules-against-alzheimer
#14
EDITORIAL
Michael Decker, Diego Muñoz-Torrero
This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27999288/melatonin-a-mitochondrial-targeting-molecule-involving-mitochondrial-protection-and-dynamics
#15
REVIEW
Dun-Xian Tan, Lucien C Manchester, Lilan Qin, Russel J Reiter
Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s)...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27997171/pyrimidine-based-inhibitors-of-dynamin-i-gtpase-activity-competitive-inhibition-at-the-pleckstrin-homology-domain
#16
Luke R Odell, Mohammed K Abdel-Hamid, Timothy A Hill, Ngoc Chau, Kelly A Young, Fiona M Deane, Jennette A Sakoff, Sofia Andersson, James A Daniel, Phillip J Robinson, Adam McCluskey
The large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). The aminopyrimidine compounds were reported to disrupt dynamin localization to the plasma membrane via the PH domain and implicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition against both dynamin I (IC50 = 10...
December 20, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27984527/agomelatine-a-new-opportunity-to-reduce-neuropathic-pain-preclinical-evidence
#17
Chouki Chenaf, Eric Chapuy, Frédéric Libert, Fabien Marchand, Christine Courteix, Marianne Bertrand, Cecilia Gabriel, Elisabeth Mocaër, Alain Eschalier, Nicolas Authier
Antidepressants are first-line treatments of neuropathic pain but not all these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect norepinephrine release. Melatonin, serotonin, and norepinephrine have been involved in the pathophysiology of neuropathic pain. Yet, no study has been conducted to determine agomelatine effects on neuropathic pain in animal models. Using 3 rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, we investigated the antihypersensitivity effect of acute and repeated agomelatine administration...
January 2017: Pain
https://www.readbyqxmd.com/read/27984170/autism-genes-are-selectively-targeted-by-environmental-pollutants-including-pesticides-heavy-metals-bisphenol-a-phthalates-and-many-others-in-food-cosmetics-or-household-products
#18
REVIEW
C J Carter, R A Blizard
The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin)...
October 27, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27934652/tryptophan-intake-in-the-us-adult-population-is-not-related-to-liver-or-kidney-function-but-is-associated-with-depression-and-sleep-outcomes
#19
REVIEW
Harris R Lieberman, Sanjiv Agarwal, Victor L Fulgoni
BACKGROUND: Tryptophan is an indispensable amino acid and is a precursor of the neurotransmitter serotonin. Tryptophan metabolites, such as serotonin and melatonin, are thought to participate in the regulation of mood and sleep and tryptophan is used to treat insomnia, sleep apnea, and depression. OBJECTIVE: This study examined the intake of tryptophan and its associations with biochemical, behavioral, sleep, and health and safety outcomes in adults in a secondary analysis of a large, publicly available database of the US population...
December 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27934651/a-perspective-on-the-safety-of-supplemental-tryptophan-based-on-its-metabolic-fates
#20
REVIEW
John D Fernstrom
Over the past 50 y, tryptophan has been ingested in amounts well in excess of its dietary requirement. This use is based on extensive findings that ingesting tryptophan increases brain tryptophan concentrations, which stimulates the synthesis and release of the neurotransmitter serotonin, from which it is derived. Such increases in serotonin function may improve mood and sleep. However, tryptophan ingestion has other effects, such as increasing serotonin production in the gut, increasing serotonin concentrations in blood, stimulating the production of the hormone melatonin (a tryptophan metabolite), stimulating tryptophan metabolism via the kynurenine pathway, and possibly stimulating the production of tryptophan metabolites in the gut microbiome...
December 2016: Journal of Nutrition
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