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https://www.readbyqxmd.com/read/29218782/therapy-development-in-huntington-disease-from-current-strategies-to-emerging-opportunities
#1
REVIEW
Audrey S Dickey, Albert R La Spada
Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder in which patients typically present with uncontrolled involuntary movements and subsequent cognitive decline. In 1993, a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene was identified as the cause of this disorder. This extended CAG repeat results in production of HTT protein with an expanded polyglutamine tract, leading to pathogenic HTT protein conformers that are resistant to protein turnover, culminating in cellular toxicity and neurodegeneration...
December 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29209553/antidyskinetic-treatment-with-mtep-affects-multiple-molecular-pathways-in-the-parkinsonian-striatum
#2
Jing-Ya Lin, Zhen-Guo Liu, Cheng-Long Xie, Lu Song, Ai-Juan Yan
Parkinson's disease is characterized by dopaminergic neuron loss and dopamine (DA) depletion in the striatum. Standard treatment is still focused on the restoration of dopamine with exogenous L-Dopa, which however causes L-Dopa-induced dyskinesia (LID). Several studies have shown that antagonism of the metabotropic glutamate receptor 5 alleviates LID, but the underlying mechanisms have remained unclear. We set out to determine where this alleviation may depend on restoring the equilibrium between the two main striatofugal pathways...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/29209205/potentiation-of-morphine-induced-antinociception-by-propranolol-the-involvement-of-dopamine-and-gaba-systems
#3
Elham A Afify, Najlaa M Andijani
Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate), (visceral, acetic acid), and (inflammatory, formalin test) in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29205377/adenosine-a2a-receptors-are-required-for-glutamate-mglur5-and-dopamine-d1-receptor-evoked-erk1-2-phosphorylation-in-rat-hippocampus-involvement-of-nmda-receptor
#4
Paraskevi Krania, Eleni Dimou, Maria Bantouna, Stylianos Kouvaros, Eirini Tsiamaki, Costas Papatheodoropoulos, Konstantinos Sarantis, Fevronia Angelatou
Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic plasticity and cognition. We recently demonstrated that stimulation of mGluR5 enhances NMDAR-responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, and this reaction was enabled by adenosine A2A receptors(A2A R) (Sarantis et al.2015). In this study, by using in vitro phosphorylation and western blot analysis in hippocampal slices of male Wistar rats, we show, that mGluR5 stimulation or mGluR5/NMDARs co-stimulation, synergistically activate ERK1/2 signaling leading to c-Fos expression...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29203575/chronic-%C3%AE-9-thc-in-rhesus-monkeys-effects-on-cognitive-performance-and-dopamine-d2-d3-receptor-availability
#5
William S John, Thomas J Martin, Kiran K Solingapuram Sai, Susan H Nader, H D Gage, Akiva Mintz, Michael A Nader
Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of those deficits remain unclear. Adult male rhesus monkeys (N=6) responded in the mornings on tasks designed to assess different cognitive domains using CANTAB touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0...
December 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29198769/subtyping-of-primary-aldosteronism-with-adrenal-vein-sampling-hormone-and-side-specific-effects-of-cosyntropin-and-metoclopramide
#6
Giacomo Rossitto, Giuseppe Maiolino, Livia Lenzini, Valeria Bisogni, Teresa Maria Seccia, Maurizio Cesari, Maurizio Iacobone, Gian Paolo Rossi
BACKGROUND: Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization index in consecutive primary aldosteronism patients submitted to adrenal vein sampling. METHODS: We recruited 171 patients; of these, 149 underwent adrenal vein sampling before and after stimulation with cosyntropin (250 µg intravenous bolus, n= 53, 73% with an aldosterone-producing adenoma) or with metoclopramide (10 mg intravenous bolus, n= 96, 65% aldosterone-producing adenoma), and 32 with an aldosterone-producing adenoma were investigated for the relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine (serotonin) 4 receptor with microarrays...
November 30, 2017: Surgery
https://www.readbyqxmd.com/read/29198511/preliminary-evidence-for-an-association-between-variants-of-the-catechol-o-methyltransferase-comt-gene-and-premature-ejaculation
#7
Patrick Jern, Ada Johansson, Jana Strohmaier, Jens Treutlein, Juhana Piha, Marcella Rietschel
BACKGROUND: Studies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE). AIM: To investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE. METHODS: PE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine...
December 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29197543/role-of-dopamine-d1-receptor-in-3-fluoromethamphetamine-induced-neurotoxicity-in-mice
#8
Phuong-Tram Nguyen, Eun-Joo Shin, Duy-Khanh Dang, Hai-Quyen Tran, Choon-Gon Jang, Ji Hoon Jeong, Yu Jeung Lee, Hyo Jong Lee, Yong Sup Lee, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
3-Fluoromethamphetamine (3-FMA) is an illegal designer drug of methamphetamine (MA) derivative. Up to date, little is known about the neurotoxic potential of 3-FMA. In the present study, we investigated the role of dopamine receptors in neurotoxicity induced by 3-FMA in comparison with MA (35 mg/kg, i.p.) as a control drug. Here we found that 3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. Treatment with 3-FMA (40 mg/kg, i.p.) resulted in significant hyperthermia, oxidative stress and microgliosis (microglial differentiation into M1 phenotype) followed by pro-apoptotic changes and the induction of terminal deoxynucleotidyl transferase dUDP nick end labeling (TUNEL)-positive cells...
November 29, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29196145/effects-of-imipramine-on-cytokines-panel-in-the-rats-serum-during-the-drug-treatment-and-discontinuation
#9
M Kuśmider, A Faron-Górecka, P Pabian, J Solich, M Szlachta, M Kolasa, D Żurawek, J Wójcikowski, W Daniel, M Dziedzicka-Wasylewska
Time dependent sensitization (TDS) - phenomenon described originally by Chiodo and Antelman (1980) in context of dopamine receptors, refers to cascade of events that continue to develop in the organism, after the initiating stimulus is no longer available. Treatment could be recognized as such a initiating stimulus (in case of depression, example of electroconvulsive therapy would be obvious, but some aspects of pharmacotherapy too). The process leads to improvement, but, on the other hand, phenomena of kindling in recurrent depression is well known (more relapses and therapies make heavier and longer lasting subsequent episodes)...
November 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29187664/-clinical-characteristics-of-hemichorea-associated-with-non-ketotic-hyperglycemia-in-3-patients-case-report-and-literature-review
#10
Yacen Hu, Yafang Zhou, Fang Yi, Lingyan Yao, Hongwei Xu, Lin Zhou
To investigate the pathophysiology, clinical manifestation and neuroimaging characteristics and therapeutic experiences for hemichore associated with non-ketotic hyperglycemia (HC-NH).
 Methods: Clinical data of three patients with HC-NH from Xiangya Hospital, Central South University were analyzed retrospectively, and the related literature was reviewed.
 Results: The core clinical features of HC-NH were characterized by acute/subacute onset of hemichorea with non-ketotic hyperglycemia in the elderly females...
November 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29182037/drd4-exon-3-genotype-and-adhd-randomized-pharmacodynamic-investigation-of-treatment-response-to-methylphenidate
#11
Darya Naumova, Natalie Grizenko, Sarojini M Sengupta, Ridha Joober
OBJECTIVES: Dopamine plays an important role in modulating attention and motor behaviors, dimensions altered in attention deficit/hyperactivity disorder (ADHD). Numerous association studies have linked dopamine receptor 4 (DRD4) to increased risk of ADHD. This study investigated the effect of DRD4 exon 3 polymorphism on child behaviours in response to treatment with methylphenidate (MPH). METHODS: 374 children diagnosed with ADHD (ages 6-12) were evaluated under three experimental conditions: baseline, placebo and MPH (0...
November 28, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29181280/associations-of-igf2-and-drd2-polymorphisms-with-laying-traits-in-muscovy-duck
#12
Qiao Ye, Jiguo Xu, Xinfeng Gao, Hongjia Ouyang, Wei Luo, Qinghua Nie
Insulin-like growth factor 2 (IGF2) and dopamine receptor 2 (DRD2) play important roles in ovarian follicular development. In this study, we analyzed tissue-specific expression of the Muscovy duck IGF2 and DRD2 genes and cloned those genes transcripts. Polymorphisms in these genes were tightly linked with egg production traits and both genes were highly expressed in the ovary. Moreover, we identified five single nucleotide polymorphisms (SNPs) for IGF1 and 28 for DRD2. Mutations A-1864G and C-1704G of IGF2 were positively correlated with increased egg laying at 59 weeks (E59W) (P < 0...
2017: PeerJ
https://www.readbyqxmd.com/read/29180955/dissociable-role-of-corticotropin-releasing-hormone-receptor-subtype-1-on-dopaminergic-and-d1-dopaminoceptive-neurons-in-cocaine-seeking-behavior
#13
Rick E Bernardi, Laura Broccoli, Natalie Hirth, Nicholas J Justice, Jan M Deussing, Anita C Hansson, Rainer Spanagel
The ability of many drugs of abuse, including cocaine, to mediate reinforcement and drug-seeking behaviors is in part mediated by the corticotropin-releasing hormone (CRH) system, in which CRH exerts its effects partly via the CRH receptor subtype 1 (CRHR1) in extra-hypothalamic areas. In fact, CRHR1 expressed in regions of the mesolimbic dopamine (DA) system have been demonstrated to modify cocaine-induced DA release and alter cocaine-mediated behaviors. Here we examined the role of neuronal selectivity of CRHR1 within the mesolimbic system on cocaine-induced behaviors...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29174638/upregulation-of-ccl7-and-ccl2-in-reward-system-mediated-through-dopamine-d1-receptor-signaling-underlies-methamphetamine-induced-place-preference-in-mice
#14
Fumihiro Saika, Norikazu Kiguchi, Naoki Wakida, Daichi Kobayashi, Yohji Fukazawa, Shinsuke Matsuzaki, Shiroh Kishioka
We previously showed that the CC-chemokine ligand 2 (CCL2)-CC-chemokine receptor 2 (CCR2) system is responsible for conditioned place preference (CPP) by methamphetamine (Meth). In this study, we investigated the roles for other chemokines mediating Meth-induced CPP and the upstream factors upregulating chemokines in mice. We found that CCL7 mRNA level was upregulated in the prefrontal cortex (PFC) after Meth administration (3mg/kg, subcutaneous), and increased CCL7 immunoreactivity was localized to the PFC NeuN-positive neurons...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29174435/dopamine-in-high-risk-populations-a-comparison-of-subjects-with-22q11-2-deletion-syndrome-and-subjects-at-ultra-high-risk-for-psychosis
#15
Claudia Vingerhoets, Oswald J N Bloemen, Erik Boot, Geor Bakker, Mariken B de Koning, Fabiana da Silva Alves, Jan Booij, Thérèse A M J van Amelsvoort
Striatal dopamine (DA) dysfunction has been consistently reported in psychotic disorders. Differences and similarities in the pathogenesis between populations at clinical and genetic risk for developing psychosis are yet to be established. Here we explored markers of dopamine (DA) function in subjects meeting clinically ultra-high risk criteria for psychosis (UHR) and in subjects with 22q11.2 deletion syndrome (22q11DS), a genetic condition associated with significant risk for developing psychotic disorders...
November 21, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29166600/dopamine-receptor-damb-signals-via-gq-to-mediate-forgetting-in-drosophila
#16
Sophie Himmelreich, Ikuo Masuho, Jacob A Berry, Courtney MacMullen, Nickolas K Skamangas, Kirill A Martemyanov, Ronald L Davis
Prior studies have shown that aversive olfactory memory is acquired by dopamine acting on a specific receptor, dDA1, expressed by mushroom body neurons. Active forgetting is mediated by dopamine acting on another receptor, Damb, expressed by the same neurons. Surprisingly, prior studies have shown that both receptors stimulate cyclic AMP (cAMP) accumulation, presenting an enigma of how mushroom body neurons distinguish between acquisition and forgetting signals. Here, we surveyed the spectrum of G protein coupling of dDA1 and Damb, and we confirmed that both receptors can couple to Gs to stimulate cAMP synthesis...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29165386/alterations-in-rat-accumbens-endocannabinoid-and-gaba-content-during-fentanyl-treatment-the-role-of-ghrelin
#17
Magdalena Sustkova-Fiserova, Chrysostomos Charalambous, Tereza Havlickova, Marek Lapka, Pavel Jerabek, Nina Puskina, Kamila Syslova
The opioid-induced rise of extracellular dopamine, endocannabinoid anandamide and γ-aminobutyric acid (GABA) concentrations triggered by opioids in the nucleus accumbens shell (NACSh) most likely participate in opioid reward. We have previously demonstrated that systemic administration of ghrelin antagonist (JMV2959) significantly decreased morphine-induced dopamine and anandamide (N-arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist. The aim of this study was to test whether JMV2959, a growth hormone secretagogue receptor (GHS-R1A) antagonist, can influence the fentanyl-induced effects on anandamide, 2-arachidonoylglycerol (2-AG) and GABA in the NACSh and specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and nucleus accumbens (NAC)...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29162966/a-qsar-model-of-olanzapine-derivatives-as-potential-inhibitors-for-5-ht2a-receptor
#18
Pooja Mitra, Aishwarya Rastogi, Mayank Rajpoot, Ajay Kumar, Vivek Srivastava
Schizophrenia is a complex, chronic mental disorder, affecting about 21 million people worldwide. It is characterized by symptoms, including distortions in thinking, perception, emotions, disorganized speech, sense of self and behavior. Recently, a numbers of marketed drugs for Schizophrenia are available against dopamine D2 and serotonin 5-HT2A receptors. Here, we docked Olanzapine derivatives (collected from literature) with 5-HT2A Receptor using the program AutoDock 4.2. The docked protein inhibitor complex structure was optimized using molecular dynamics simulation for 5ps with the CHARMM-22 force field using NAMD (NAnoscale Molecular Dynamics program) incorporated in visual molecular dynamics (VMD 1...
2017: Bioinformation
https://www.readbyqxmd.com/read/29156812/correlation-of-drd2-mrna-expression-levels-with-deficit-syndrome-severity-in-chronic-schizophrenia-patients-receiving-clozapine-treatment
#19
Liang Liu, Yin Luo, Guofu Zhang, Chunhui Jin, Zhenhe Zhou, Zaohuo Cheng, Guozhen Yuan
Schizophrenia is a complex, severe, chronic psychiatric disorder, and the associated deficit syndrome is widely regarded as an important clinical aspect of schizophrenia. This study analyzed the relationship of deficit syndrome severity with the mRNA levels of members of signaling pathways that associate with the pathophysiology of schizophrenia, including the dopamine D2 receptor (DRD2), protein kinase B (AKT1), and phosphoinositide-3 kinase (PI3KCB), in peripheral blood leukocytes (PBLs) of 20 healthy controls and 19 chronic schizophrenia patients with long-term clozapine treatment...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#20
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
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