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https://www.readbyqxmd.com/read/29786666/dopamine-receptor-subtypes-differentially-regulate-autophagy
#1
Dongmei Wang, Xinmiao Ji, Juanjuan Liu, Zhiyuan Li, Xin Zhang
Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that dopamine receptors D2 and D3 (D2-like family) are positive regulators of autophagy, while dopamine receptors D1 and D5 (D1-like family) are negative regulators. Furthermore, dopamine and ammonia, the two reported endogenous ligands of dopamine receptors, both can induce dopamine receptor internalization and degradation. In addition, we found that AKT (protein kinase B)-mTOR (mechanistic target of rapamycin) and AMPK (AMP-activated protein kinase) pathways are involved in DRD3 (dopamine receptor D3) regulated autophagy...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783994/large-scale-transcriptomic-analysis-reveals-that-pridopidine-reverses-aberrant-gene-expression-and-activates-neuroprotective-pathways-in-the-yac128-hd-mouse
#2
Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman, Michael R Hayden
BACKGROUND: Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782864/are-dopamine-receptor-and-transporter-changes-in-rett-syndrome-reflected-in-mecp2-deficient-mice
#3
Dean F Wong, Mary E Blue, James R Brašić, Ayon Nandi, Heather Valentine, Kirstie H Stansfield, Olivier Rousset, Genila Bibat, Mary E Yablonski, Michael V Johnston, Albert Gjedde, SakkuBai Naidu
In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2 R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1 R and D2 R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2 R density in the striatum of women with RTT compared to control subjects...
May 18, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29780881/nucleus-accumbens-microcircuit-underlying-d2-msn-driven-increase-in-motivation
#4
Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, Ana João Rodrigues
The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29779156/adolescent-isolation-rearing-produces-a-prepulse-inhibition-deficit-correlated-with-expression-of-the-nmda-glun1-subunit-in-the-nucleus-accumbens
#5
Megan L Fitzgerald, Virginia M Pickel
Adolescence is a transition period during which social interaction is necessary for normal brain and behavior development. Severely abnormal social interactions during adolescence can increase the incidence of lifelong psychiatric disease. Decreased prepulse inhibition (PPI) is a quantifiable hallmark of some psychiatric illnesses in humans and can be elicited in rodents by isolation rearing throughout the adolescent transition period. PPI is a measure of sensorimotor gating in which the nucleus accumbens (Acb) is crucially involved...
May 19, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#6
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29775777/antidepressant-potential-of-novel-flavonoids-derivatives-from-sweet-violet-viola-odorata-l-pharmacological-biochemical-and-computational-evidences-for-possible-involvement-of-serotonergic-mechanism
#7
Nasiara Karim, Imran Khan, Abeer Abdelhalim, Ajmal Khan, Sobia Ahsan Halim
Plant-derived natural constituents are of great interest in modern drug discovery due to their natural diversity. Viola odorata L has been traditionally used for the treatment of neuropsychiatric disorders. The present study was undertaken to isolate phytoconstituents including three flavonoids 5,7-Dihydroxy-3,6-dimethoxyflavone[1] 5,7,4'-trihydroxy-3',5'dimethoxyflavone [2] and 5,7,4'-trihydroxy-3'-methoxyflavone [3] from the whole plant of Viola odorata L and to investigate the antidepressant-like effects of these compounds and their possible mechanism of action using antagonists of the serotonergic, dopaminergic and adrenergic system...
May 15, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29775630/the-basolateral-amygdala-dopaminergic-system-contributes-to-the-improving-effect-of-nicotine-on-stress-induced-memory-impairment-in-rats
#8
Elnaz Keshavarzian, Zahra Ghasemzadeh, Ameneh Rezayof
Stress seems to be an important risk factor in the beginning and continuing stages of cigarette tobacco smoking in humans. Considering that both of nicotine administration and stress exposure affect cognitive functions including memory formation, the aim of the present study was 1) to evaluate the effect of subcutaneous (s.c.) administration of nicotine on memory formation under stress and 2) to assess the possible role of the basolateral amygdala (BLA) dopamine D1 and D2 receptors in the effect of nicotine on stress-induced memory retrieval impairment...
May 15, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29772497/the-role-of-the-vasopressin-system-and-dopamine-d1-receptors-in-the-effects-of-social-housing-condition-on-morphine-reward
#9
M L Shawn Bates, Rebeca S Hofford, Michael A Emery, Paul J Wellman, Shoshana Eitan
BACKGROUND: The association with opioid-abusing individuals or even the perception of opioid abuse by peers are risk factors for the initiation and escalation of abuse. Similarly, we demonstrated that morphine-treated animals housed with only morphine-treated animals (referred to as morphine only) acquire morphine conditioned place-preference (CPP) more readily than morphine-treated animals housed with drug-naïve animals (referred to as morphine cage-mates). However, the molecular mechanisms underlying these effects are still elusive...
April 22, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#10
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29767374/the-effect-of-ca1-dopaminergic-system-on-amnesia-induced-by-harmane-in-mice
#11
Mohammad Nasehi, Simin Hasanvand, Fatemeh Khakpai, Mohammad-Reza Zarrindast
In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0...
May 16, 2018: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/29765540/could-a-plant-derived-protein-potentiate-the-anticancer-effects-of-a-stem-cell-in-brain-cancer
#12
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Cost, Heron Fernandes Vieira Torquato, Natalia Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma is the most aggressive brain tumor with poor overall survival bellow 2 years. The natural compounds with anti-cancer properties, are thus gaining attention for possible adjuvant GBM treatment. In various cancer models Enterolobium contortisiliquum Trypsin Inhibitor (EcTI) proved to have anti-cancer effects. Here, we investigated the EcTI effects on GBM U87 cells and on mesenchymal stem cells (MSC) compared to their direct coculture (MSC/U87). MSC are present in tumor stroma, modulating GBM cells phenotype, and also represent potential drug delivery vehicle due to their tumor tropism...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764507/aldolase-a-promotes-proliferation-and-g-1-s-transition-via-the-egfr-mapk-pathway-in-non-small-cell-lung-cancer
#13
Hailu Fu, Huijun Gao, Xiaoyu Qi, Lei Zhao, Donghua Wu, Yuxin Bai, Huimin Li, Xuan Liu, Jun Hu, Shujuan Shao
BACKGROUND: Our previous study demonstrated that aldolase A (ALDOA) is overexpressed in clinical human lung squamous cell carcinoma and that ALDOA promotes epithelial-mesenchymal transition and tumorigenesis. The present study aimed to explore the function of ALDOA in the modulation of non-small cell lung cancer (NSCLC) proliferation and cell cycle progression and the potential mechanism. METHODS: ALDOA was knocked down by short hairpin RNA in H520 and H1299 cells...
May 8, 2018: Cancer communications
https://www.readbyqxmd.com/read/29747224/balance-of-go1%C3%AE-and-go2%C3%AE-expression-regulates-motor-function-via-the-striatal-dopaminergic-system
#14
J Baron, A Bilbao, H Hörtnagl, L Birnbaumer, S Leixner, R Spanagel, G Ahnert-Hilger, I Brunk
The heterotrimeric G-protein Go with its splice variants, Go1α and Go2α, seems to be involved in the regulation of motor function but isoform specific effects are still unclear. We found that Go1α-/- knockouts performed worse on the rota-rod than Go2α-/- and wild type (WT) mice. In Go1+2α-/- mice motor function was partially recovered. Furthermore, Go1+2α-/- mice showed an increased spontaneous motor activity. Compared to wild types or Go2α-/- mice, Go1+2α-/- mice developed increased behavioural sensitization following repetitive cocaine treatment, but failed to develop conditioned place preference...
May 10, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29743815/estrogen-receptor-modulators-genistein-daidzein-and-erb-041-inhibit-cell-migration-invasion-proliferation-and-sphere-formation-via-modulation-of-fak-and-pi3k-akt-signaling-in-ovarian-cancer
#15
Karen K L Chan, Michelle K Y Siu, Yu-Xin Jiang, Jing-Jing Wang, Thomas H Y Leung, Hextan Y S Ngan
Background: Ovarian cancer is the most lethal gynaecological malignancy. Chemotherapy is the main stay of treatment for metastatic disease, with modest response rates but significant side effects. Therefore, there is a need for alternative therapies that can control the disease while offering good quality of life. Ovarian cancer cells express both estrogen receptor subtypes (ERα and ERβ). There is growing evidence that ERβ is anti-oncogenic. Genistein and daidzein are phytoestrogens found in soybeans and they display higher affinity to bind ERβ...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29741640/rankl-rank-pathway-and-its-inhibitor-rank-fc-in-uterine-leiomyoma-growth
#16
Deborah E Ikhena, Shimeng Liu, Stacy Kujawa, Ecem Esencan, John S Coon, Jared Robins, Serdar E Bulun, Ping Yin
Context: Uterine leiomyomas are the most common type of gynecologic tumor in women. Objective: To determine the role of the cytokine receptor activator of nuclear factor κ-Β ligand (RANKL); its receptor, receptor activator of nuclear factor κ-Β (RANK); and the RANKL/RANK pathway inhibitor RANK-Fc in leiomyoma growth. Design: Messenger RNA (mRNA) or protein levels of RANKL, RANK, and proliferation markers cyclin D1 and Ki67 were assessed in various leiomyoma tissues and cell populations...
May 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29740493/bioinformatic-analysis-and-prediction-of-the-function-and-regulatory-network-of-long-non-coding-rnas-in-hepatocellular-carcinoma
#17
Ming-Rong Cao, Ze-Ping Han, Ji-Ming Liu, Yu-Guang Li, Yu-Bing Lv, Jia-Bin Zhou, Jin-Hua He
Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29740282/muscarinic-m4-receptors-on-cholinergic-and-dopamine-d1-receptor-expressing-neurons-have-opposing-functionality-for-positive-reinforcement-and-influence-impulsivity
#18
Anna M Klawonn, Daniel B Wilhelms, Sarah H Lindström, Anand Kumar Singh, Maarit Jaarola, Jürgen Wess, Michael Fritz, David Engblom
The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29737821/association-of-dopamine-receptor-d2-gene-drd2-taq1-polymorphisms-with-eating-behaviors-and-obesity-among-chinese-and-indian-malaysian-university-students
#19
Fang-Ying Lek, Hing-Huat Ong, Yee-How Say
BACKGROUND AND OBJECTIVES: This study investigated the association of DRD2 Taq1A, Taq1B and Taq1D gene polymorphisms with eating behavior, the preference/intake frequency/craving of high-fat foods and obesity in 394 Malaysian adults (161 males, 233 females; 308 Chinese, 86 Indians; 67 obese, 327 non-obese). METHODS AND STUDY DESIGN: Eating behaviors namely Cognitive Restraint, Uncontrolled Eating and Emotional Eating scores were assessed by the Three Factor Eating Questionnaire-R18...
2018: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29737363/dissociable-roles-of-the-nucleus-accumbens-d1-and-d2-receptors-in-regulating-cue-elicited-approach-avoidance-conflict-decision-making
#20
David Nguyen, Victoria Fugariu, Suzanne Erb, Rutsuko Ito
RATIONALE: Approach and avoidance decisions are made when an animal experiences a state of motivational conflict inflicted by stimuli imbued with both positive and negative valences. The nucleus accumbens (NAc), a site where valenced information and action selection converge, has recently been found to be critically involved in the resolution of approach-avoidance conflict. However, the individual roles of the region's dopamine receptor D1 (D1R)- and D2 (D2R)-expressing medium spiny neurons (MSNs) in regulating conflict resolution have not been well established...
May 8, 2018: Psychopharmacology
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