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https://www.readbyqxmd.com/read/28414692/neuronal-fibers-and-neurotransmitter-receptor-expression-in-the-human-endolymphatic-sac
#1
Martin Nue Møller, Svend Kirkeby, Jonas Vikeså, Finn Cilius Nielsen, Per Cayé-Thomasen
INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may have multiple functions, including an ion-transport capacity comparable to the kidney, an immunological capacity and a possible natriuretic capacity. Further, there have been speculations of a yet undefined role in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES...
April 14, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28404690/pharmacologic-characterization-of-valbenazine-nbi-98854-and-its-metabolites
#2
Dimitri E Grigoriadis, Evan Smith, Sam R J Hoare, Ajay Madan, Haig Bozigian
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is being developed for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)-α-dihydrotetrabenazine (R,R,R-DHTBZ) and a mono-oxy metabolite, NBI-136110. Radioligand binding studies were conducted to assess and compare valbenazine, tetrabenazine and their respective metabolites in their abilities to selectively and potently inhibit [(3)H]-DHTBZ binding to VMAT2 in rat striatal, rat forebrain, and human platelet homogenates...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28396635/spontaneously-hypertensive-rats-shr-are-resistant-to-a-reserpine-induced-progressive-model-of-parkinson-s-disease-differences-in-motor-behavior-tyrosine-hydroxylase-and-%C3%AE-synuclein-expression
#3
Anderson H F F Leão, Ywlliane S R Meurer, Anatildes F da Silva, André M Medeiros, Clarissa L C Campêlo, Vanessa C Abílio, Rovena C G K Engelberth, Jeferson S Cavalcante, Geison S Izídio, Alessandra M Ribeiro, Regina H Silva
Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28343139/oxytocin-in-corticosterone-induced-chronic-stress-model-focus-on-adrenal-gland-function
#4
Dušanka Stanić, Bosiljka Plećaš-Solarović, Duško Mirković, Predrag Jovanović, Slađana Dronjak, Bojan Marković, Tea Đorđević, Svetlana Ignjatović, Vesna Pešić
Chronic stress conditions can lead to considerable and extensible changes in physiological and psychological performances, and in emergence of risk for various somatic diseases. On the other hand, the neuropeptide oxytocin is reported to increase the resistance of the organism to stress and modulate activity of autonomic nervous system. Chronic corticosterone administration is used as a rat model for a state observed in terms of chronic stress exposure, when negative feedback mechanism of hypothalamus-pituitary-adrenal axis activity is disrupted...
March 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28341570/a-study-of-the-age-related-effects-of-lactational-atrazine-exposure
#5
Yan Sun, Yan-Shu Li, Bai Li, Kun Ma, Bai-Xiang Li
A growing number of reports have demonstrated that the widely-used herbicide Atrazine (ATR) can cause injury to dopamine (DA) neurons, but the exact mechanism remains unclear. In this study, we examined the effects of lactational ATR exposure in Sprague-Dawley rats on dopaminergic neuron health later in life. Compared with control rats, rats exposed to ATR during a critical period of neural development showed decreased striatal DA content and increased rates of DA turnover. The expression of Monoamine oxidase (MAO), which is associated with DA degradation, was up-regulated, and the expression of Vesicular Monoamine Transporter 2 (VMAT2), which is associated with DA transport, was down-regulated...
March 22, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28336296/serotonin-and-dopamine-transporter-pet-changes-in-the-premotor-phase-of-lrrk2-parkinsonism-cross-sectional-studies
#6
Daryl J Wile, Pankaj A Agarwal, Michael Schulzer, Edwin Mak, Katherine Dinelle, Elham Shahinfard, Nasim Vafai, Kazuko Hasegawa, Jing Zhang, Jessamyn McKenzie, Nicole Neilson, Audrey Strongosky, Ryan J Uitti, Mark Guttman, Cyrus P Zabetian, Yu-Shin Ding, Mike Adam, Jan Aasly, Zbigniew K Wszolek, Matthew Farrer, Vesna Sossi, A Jon Stoessl
BACKGROUND: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. METHODS: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada...
May 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28276538/valbenazine-for-the-treatment-of-tardive-dyskinesia
#7
N Barquero
Valbenazine (NBI-98854, Ingrezza) is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that modulates dopamine release during nerve communication. The pharmacological target VMAT2 may play an important role in the treatment of tardive dyskinesia (TD), an iatrogenic condition associated with the administration of antipsychotic medication for long periods and characterized by rapid, repetitive, stereotypic, involuntary movements of the face and extremities. There are currently no Food and Drug Administration (FDA)-approved drugs for the treatment of TD...
December 2016: Drugs of Today
https://www.readbyqxmd.com/read/28265459/indirect-tolerability-comparison-of-deutetrabenazine-and-tetrabenazine-for-huntington-disease
#8
Daniel O Claassen, Benjamin Carroll, Lisa M De Boer, Eric Wu, Rajeev Ayyagari, Sanjay Gandhi, David Stamler
BACKGROUND: Vesicular monoamine transporter 2 (VMAT2) inhibitors can improve hyperkinetic movements, and are effective treatment options for chorea of Huntington disease (HD). Tetrabenazine was assessed for treating chorea in the TETRA-HD trial, and while efficacious, there are tolerability concerns possibly due to its pharmacokinetic properties. Deutetrabenazine is a novel VMAT2 inhibitor that contains deuterium, which extends active metabolite half-lives and minimizes drug concentration fluctuations...
2017: Journal of Clinical Movement Disorders
https://www.readbyqxmd.com/read/28257461/quantitative-analysis-of-the-therapeutic-effect-of-magnolol-on-mptp-induced-mouse-model-of-parkinson-s-disease-using-in-vivo-18f-9-fluoropropyl-dihydrotetrabenazine-pet-imaging
#9
Chi-Chang Weng, Zi-An Chen, Ko-Ting Chao, Ting-Wei Ee, Kun-Ju Lin, Ming-Huan Chan, Ing-Tsung Hsiao, Tzu-Chen Yen, Mei-Ping Kung, Ching-Han Hsu, Shiaw-Pyng Wey
18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i...
2017: PloS One
https://www.readbyqxmd.com/read/28214749/impairment-in-the-mesohippocampal-dopamine-circuit-following-exposure-to-the-brominated-flame-retardant-hbcdd
#10
Camille Pham-Lake, Elizabeth B Aronoff, Chad R Camp, Aimee Vester, Sam J Peters, W Michael Caudle
Many chemicals have been used to increase the safety of consumer products by reducing their flammability and risk for ignition. Recent focus on brominated flame retardants, such as polybrominated diphenyl ethers (PBDEs) has shown them to contribute to neurobehavioral deficits in children, including learning and memory. As the manufacture and use of PBDEs have been reduced, replacement chemicals, such as hexabromocyclododecane (HBCDD) have been substituted. Our current study evaluated the neurotoxicity of HBCDD, concentrating on dopaminergic innervation to the hippocampus...
March 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28213878/cotransfecting-norepinephrine-transporter-and-vesicular-monoamine-transporter-2-genes-for-increased-retention-of-metaiodobenzylguanidine-labeled-with-iodine-131-in-malignant-hepatocarcinoma-cells
#11
Yanlin Zhao, Xiao Zhong, Xiaohong Ou, Huawei Cai, Xiaoai Wu, Rui Huang
Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine ((131)I-MIBG) in non-neuroendocrine tumors. However, the use of (131)I-MIBG is limited by its short retention time in target cells. To prolong the retention of (131)I-MIBG in target cells, we infected hepatocarcinoma (HepG2) cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 (VMAT2) genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines...
February 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28192111/effects-of-progesterone-administered-after-mptp-on-dopaminergic-neurons-of-male-mice
#12
Nadhir Litim, Marc Morissette, Thérèse Di Paolo
Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28161459/peptide-microarray-based-characterization-of-antibody-responses-to-host-proteins-after-bacille-calmette-gu%C3%A3-rin-vaccination
#13
REVIEW
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28094812/putative-presynaptic-dopamine-dysregulation-in-schizophrenia-is-supported-by-molecular-evidence-from-post-mortem-human-midbrain
#14
T D Purves-Tyson, S J Owens, D A Rothmond, G M Halliday, K L Double, J Stevens, T McCrossin, C Shannon Weickert
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28046395/su-f-t-590-modeling-ptv-dose-fall-off-for-cervical-cancer-sbrt-treatment-planning-using-vmat-and-step-and-shoot-imrt
#15
A Brito Delgado, D Cohen, T Eng, A Gutierrez
PURPOSE: Due to the high dose per fraction in SBRT, dose conformity and dose fall-off are critical. In patients with cervical cancer, rapid dose fall-off is particularly important to limit dose to the nearby rectum, small bowel, and bladder. This study compares the target volume dose fall-off for two radiation delivery techniques, fixed-field IMRT & VMAT, using non-coplanar beam geometries. Further comparisons are made between 6 and 10MV photon beam energies. METHODS: Eleven (n=11) patients were planned in Pinnacle3 v9...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28044943/forgotten-but-not-gone-new-developments-in-the-understanding-and-treatment-of-tardive-dyskinesia
#16
Jonathan M Meyer
The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data...
December 2016: CNS Spectrums
https://www.readbyqxmd.com/read/27986625/gz-793a-inhibits-the-neurochemical-effects-of-methamphetamine-via-a-selective-interaction-with-the-vesicular-monoamine-transporter-2
#17
Justin R Nickell, Kiran B Siripurapu, David B Horton, Guangrong Zheng, Peter A Crooks, Linda P Dwoskin
Lobeline and lobelane inhibit the behavioral and neurochemical effects of methamphetamine via an interaction with the vesicular monoamine transporter-2 (VMAT2). However, lobeline has high affinity for nicotinic receptors, and tolerance develops to the behavioral effects of lobelane. A water-soluble analog of lobelane, R-N-(1,2-dihydroxypropyl)-2,6-cis-di-(4-methoxyphenethyl)piperidine hydrochloride (GZ-793A), also interacts selectively with VMAT2 to inhibit the effects of methamphetamine, but does not produce behavioral tolerance...
December 13, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27966075/protective-effect-of-curcumin-by-modulating-bdnf-darpp32-creb-in-arsenic-induced-alterations-in-dopaminergic-signaling-in-rat-corpus-striatum
#18
Pranay Srivastava, Yogesh K Dhuriya, Richa Gupta, Rajendra K Shukla, Rajesh S Yadav, Hari N Dwivedi, Aditya B Pant, Vinay K Khanna
Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls...
December 13, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27965546/spatial-and-temporal-distribution-of-dopaminergic-neurons-during-development-in-zebrafish
#19
Yuchen Du, Qiang Guo, Minghui Shan, Yongmei Wu, Sizhou Huang, Haixia Zhao, Huarong Hong, Ming Yang, Xi Yang, Liyi Ren, Jiali Peng, Jing Sun, Hongli Zhou, Shurong Li, Bingyin Su
As one of the model organisms of Parkinson's disease (PD) research, the zebrafish has its advantages, such as the 87% homology with human genome and transparent embryos which make it possible to observe the development of dopaminergic neurons in real time. However, there is no midbrain dopaminergic system in zebrafish when compared with mammals, and the location and projection of the dopaminergic neurons are seldom reported. In this study, Vmat2:GFP transgenic zebrafish was used to observe the development and distribution of dopaminergic neurons in real time...
2016: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/27924069/retrograde-trafficking-of-vmat2-and-its-role-in-protein-stability-in-non-neuronal-cells
#20
Qiuzi Wu, Hongfei Xu, Wei Wang, Fei Chang, Yu Jiang, Yongjian Liu
Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2 (VMAT2) contributes to the pathogenesis of Parkinson's disease. That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases. However, whether VMAT2 function is regulated by retrograde trafficking is unknown. By using biochemistry and cell biology approaches, we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells...
November 2016: Journal of Biomedical Research
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