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Maurizio Manca, Veridiana Pessoa, Ana Illera Lopez, Patrick T Harrison, Fabio Miyajima, Helen Sharp, Andrew Pickles, Jonathan Hill, Chris Murgatroyd, Vivien J Bubb, John P Quinn
The monoamine oxidase A (MAOA) uVNTR (upstream variable number tandem repeat) is one of the most often cited examples of a gene by environment interaction (GxE) in relation to behavioral traits. However, MAOA possesses a second VNTR, 500 bp upstream of the uVNTR, which is termed d- or distal VNTR. Furthermore, genomic analysis indicates that there are a minimum of two transcriptional start sites (TSSs) for MAOA, one of which encompasses the uVNTR within the 5' untranslated region of one of the isoforms. Through expression analysis in semi-haploid HAP1 cell lines genetically engineered in order to knockout (KO) either the uVNTR, dVNTR, or both VNTRs, we assessed the effect of the two MAOA VNTRs, either alone or in combination, on gene expression directed from the different TSSs...
March 14, 2018: Journal of Molecular Neuroscience: MN
Samuel Carbunaru, Robert S Eisinger, Adolfo Ramirez-Zamora, Dana Bassan, Amin Cervantes-Arriaga, Mayela Rodriguez-Violante, Daniel Martinez-Ramirez
Objectives: Impulse control disorders (ICDs) are common among patients with Parkinson's disease (PD). Risk factors identified for developing ICDs include young age, family history, and impulsive personality traits. However, the association of these potentially disabling disorders with nondopaminergic drugs and sleep disorders has been understudied. Our objective was to examine the association between ICDs and nondopaminergic medications and sleep disorders. Methods: We conducted an observational study of 53 patients with PD from the National Institute of Neurology and Neurosurgery...
March 2018: Brain and Behavior
Arezou Sayad, Rezvan Noroozi, Zahra Khodamoradi, Mir Davood Omrani, Mohammad Taheri, Soudeh Ghafouri-Fard
Genetic association studies have linked suicide behavior with genes encoding transporters of monoamine. Variants in the vesicular monoamine transporter 1 (VMAT1) have been previously shown to be associated with several psychiatric disorders including schizophrenia and bipolar disorder. However, their association with suicide behavior has not been explored. In the present study, we genotyped three single-nucleotide polymorphisms (rs2270637, rs1390938, and rs2279709) within this gene in 100 individuals who attempted suicide, 236 suicide victims, and 300 control subjects without any history of psychiatric disorders or suicide ideation...
March 14, 2018: Journal of Molecular Neuroscience: MN
Zhaoqun Liu, Lingling Wang, Zhao Lv, Zhi Zhou, Weilin Wang, Meijia Li, Qilin Yi, Limei Qiu, Linsheng Song
It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a "nervous-hemocyte"-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system...
2018: Frontiers in Immunology
Bhupinder Kumar, Mohit Kumar, Ashish Ranjan Dwivedi, Vinod Kumar
Monoamine oxidase B (MAO-B) inhibitors are potential drug candidates for the treatment of various neurological disorders including Parkinson's disease. A total of 20 new propargyl-containing 2,4,6-trisubstituted pyrimidine derivatives were synthesized and screened for MAO inhibition using Amplex Red assays. All the synthesized compounds were found to be reversible and selective inhibitors of the MAO-B isoform at sub-micromolar concentrations. MVB3 was the most potent MAO-B inhibitor with an IC50 value of 0...
March 13, 2018: ChemMedChem
Frederico Favaro Ribeiro, Francisco Jaime Bezerra Mendonca, Jahan B Ghasemi, Hamilton M Ishiki, Marcus Tullius Scotti, Luciana Scotti
Since antiquity, humanity has used medicinal plant preparations to cure its ills, and, as research has progressed, new technologies have enabled more investigations on natural compounds which originate from plants, fungi, and marine species. The health benefits that these natural products provide have become a motive for treatment studies of various diseases. Among them, the neurodegenerative diseases like Alzheimer's and Parkinson's, a major age-related neurodegenerative disorder. Studies with natural products for neurodegenerative diseases (particularly through molecular docking) search for, and then focus on those ligands which offer effective inhibition of the enzymes monoamine oxidase and acetylcholinesterase...
March 13, 2018: Combinatorial Chemistry & High Throughput Screening
Michael Strupp, Ludwig Kraus, Franz Schautzer, Dan Rujescu
OBJECTIVES: Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD). METHODS: Thirteen adults aged 40-75 years (mean 58.9 years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1 year...
March 12, 2018: Journal of Neurology
Chi-Hyeon Yoo, Song-I Lim, Kyu-Ho Song, Dong-Cheol Woo, Bo-Young Choe
Although recent investigations of major depressive disorder (MDD) have focused on the monoaminergic system, accumulating evidences suggest that alternative pathophysiological models of MDD and treatment options for patients with MDD are needed. Animals subjected to chronic forced swim stress (CFSS) develop behavioral despair. The purpose of this study was to investigate the in vivo effects of CFSS on systems other than the monoamine system in the rat prefrontal cortex (PFC) with 7T and short-echo-time (16.3 ms) proton magnetic resonance spectroscopy (1 H MRS)...
March 9, 2018: Neurochemistry International
Tetsuo Kiso, Ai Moriyama, Masako Furutani, Ritsuko Matsuda, Yukiko Funatsu
Dysfunction of the monoamine systems in the nervous system is associated with the clinical symptoms of fibromyalgia. Reserpine-induced myalgia (RIM) rats are a putative model of fibromyalgia in which muscle pressure thresholds and monoamine content is reduced in the brain and spinal cord. We examined the effects of pregabalin and duloxetine, drugs approved for fibromyalgia treatment, on the levels of extracellular neurotransmitters in the dorsal horn of the spinal cord in RIM rats using microdialysis. Male SD rats were used for all experiments...
March 9, 2018: European Journal of Pharmacology
Brianna J Shinn, Laura J Tafe, Pantila Vanichakarn
BACKGROUND Carcinoid tumor, benign, low-grade malignant, and high-grade malignant, can be associated with the release of vasoactive substances that cause symptoms including cutaneous flushing, diarrhea, and bronchospasm. In 50-60% of patients with carcinoid syndrome, the vasoactive substances cause fibrosis of the pulmonary and tricuspid heart valves which lead to regurgitation and right-sided heart failure. The right side of the heart is usually affected because monoamine oxidases in the lungs usually inactivate the vasoactive substances...
March 12, 2018: American Journal of Case Reports
Hiroko Tsunekawa, Kazue Takahata, Motoki Okano, Toshiko Ishikawa, Hiroshi Satoyoshi, Tetsuya Nishimura, Naoya Hoshino, Shizuko Muraoka
3,4-Dihydroxy-L-phenylalanine (L-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia. Here, using unilateral 6-hydroxydopamine-lesioned rats showing degeneration of nigrostriatal dopaminergic neurons and L-Dopa-induced motor complications, we determined the efficacy of selegiline in controlling L-Dopa-induced motor fluctuations and exacerbated dyskinesia...
March 8, 2018: Behavioural Brain Research
Kathy Y Liu, Aisling E Stringer, Suzanne J Reeves, Robert J Howard
OBJECTIVE: To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD). METHODS: Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate. RESULTS: Forty-five studies were included...
March 7, 2018: Ageing Research Reviews
Allison A Feduccia, Michael C Mithoefer
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers...
March 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Nicki Niemann, Joseph Jankovic
The dose (mg/day) for Clonazepam which reads.
March 10, 2018: Drugs
Manoj Kumar, Tarek Trabelsi, Joseph S Francisco
Urea is ubiquitous in rainwaters and aqueous aerosols in different environments. However, its atmospheric fate and the exact mechanism on how it influences new particle formation remains completely unexplored. Herein, we have used quantum chemical calculations and Born Oppenheimer molecular dynamics simulations to explore the potential role of urea in the particle formation events. The results suggest that urea binds more strongly to common acidic precursors than ammonia or monoamines and is capable of binding at most two molecules of an acidic precursor or hydroperoxyl radical via hydrogen bonding interactions...
March 9, 2018: Journal of Physical Chemistry. A
Souravh Bais, Renu Kumari, Yash Prashar
BACKGROUND: sinapic acid (3, 5 di-methoxy 4-hydroxycinnamic acid) is a bioactive compound. Recent studies showed that it has a significant potential to attenuate various chemically induced Neurodegenerative toxicities. AIM: the present study investigates the potential of sinapic acid as neuromodulator and its effect on release of Monoamine Oxidase (MAO-A, MAO-B), TNF-α, Acetylcholine esterase Enzyme, in cognitive dysfunctions associated with experimental dementia...
March 9, 2018: CNS & Neurological Disorders Drug Targets
R B Raffa, J V Pergolizzi, R Taylor, M H Ossipov
WHAT IS KNOWN AND OBJECTIVE: Advances in pain research have led to an understanding that many pains are driven by more than one underlying (patho)physiologic cause (ie, they are "multimechanistic") and that better pain relief is obtained with fewer adverse effects when an analgesic is correspondingly multimechanistic. At least two of the more-modern analgesics combine opioid and non-opioid mechanisms, and have become known as "atypical opioids." Less well known is that just as Nature evolved opioids, it also evolved atypical opioids, presaging modern drug discovery efforts...
March 8, 2018: Journal of Clinical Pharmacy and Therapeutics
Tanja Scherer, Gabriella Allegri, Christineh N Sarkissian, Ming Ying, Hiu Man Grisch-Chan, Anahita Rassi, Shelley R Winn, Cary O Harding, Aurora Martinez, Beat Thöny
Hyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4 ) treatment in Pahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type...
March 8, 2018: Journal of Inherited Metabolic Disease
Yu Sun, Ning Zhao, Wangyuan Liu, Miao Liu, Zizhao Ju, Jun Li, Zhen Cheng, Xingdang Liu
PURPOSE: To investigate the relationship between expression level of vesicular monoamine transporter 2 (VMAT2) and myopia, as well as the feasibility of noninvasive myopia diagnosis through imaging VMAT2 in retina by using [18 F]fluoropropyl-(+)-dihydrotetrabenazine ([18 F]FP-(+)-DTBZ). PROCEDURES: The right eyes of ten guinea pigs were deprived of vision to establish form-deprived (FD) myopia and the left eyes were untreated as the self-control eyes. The location and expression level of VMAT2 in the eyes were detected by micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging through using [18 F]FP-(+)-DTBZ...
March 8, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Bombi Lee, Insop Shim, Hyejung Lee, Dae-Hyun Hahm
Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure...
March 2018: Korean Journal of Physiology & Pharmacology
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