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https://www.readbyqxmd.com/read/29644470/ruthenium-ii-n-alkyl-phenothiazine-complexes-as-potential-anticancer-agents
#1
Andreja Leskovac, Sandra Petrovic, Tamara Lazarevic-Pasti, Milena Krstic, Vesna Vasic
In recent years, the search for effective anticancer compounds based on transition metal complexes has been the focus of medical investigations. The synergy between the ruthenium(II) and N-alkylphenothiazine counter-ions (chlorpromazine hydrochloride, thioridazine hydrochloride and trifluoperazine dihydrochloride, respectively) through the formation of three different complexes (1-3) was investigated. We explored whether the selected counter-ions and complexes might affect redox homeostasis and genome integrity of normal human blood cells, and induce an inhibition of Na+ /K+ -ATPase and AChE at pharmacologically relevant doses...
April 11, 2018: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29643379/publisher-correction-role-of-dopamine-d2-receptor-in-stress-induced-myelin-loss
#2
Mi-Hyun Choi, Ji Eun Na, Ye Ran Yoon, Hyo Jin Lee, Sehyoun Yoon, Im Joo Rhyu, Ja-Hyun Baik
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29642911/gnrh-dysregulation-in-polycystic-ovarian-syndrome-pcos-is-a-manifestation-of-an-altered-neurotransmitter-profile
#3
Nirja Chaudhari, Mitali Dawalbhakta, Laxmipriya Nampoothiri
BACKGROUND: GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS...
April 11, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29627696/effects-of-the-141c-insertion-deletion-polymorphism-in-the-dopamine-d2-receptor-gene-on-the-dopamine-system-in-the-striatum-in-patients-with-schizophrenia
#4
Junya Matsumoto, Atsuko Nagaoka, Yasuto Kunii, Itaru Miura, Mizuki Hino, Shin-Ichi Niwa, Hiroyuki Nawa, Hitoshi Takahashi, Akiyoshi Kakita, Hirooki Yabe
The relationships between -141C insertion/deletion (Ins/Del) polymorphisms in the dopamine D2 receptor gene and the two dopamine system integrators, i.e., dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN), are still unclear. In this study, we assessed the effect of this polymorphism on DARPP-32 and CaN protein expression in the postmortem striatum of patients with schizophrenia and control individuals. The expression levels of truncated DARPP and CaN were lower in Del allele carriers...
March 29, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29626485/rapid-effects-of-ovarian-hormones-in-dorsal-striatum-and-nucleus-accumbens
#5
REVIEW
Katie E Yoest, Jacqueline A Quigley, Jill B Becker
Estradiol and progesterone rapidly induce changes in dopaminergic signaling within the dorsal striatum and nucleus accumbens of female rats. In ovariectomized females, estradiol rapidly enhances dopamine release and modulates binding of dopamine receptors. Progesterone further potentiates the effect of estradiol on dopamine release. The effects of both estradiol and progesterone are time course dependent, with increases in dopamine release immediately after acute hormone administration followed by later inhibition of dopamine release...
April 4, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29626009/the-nurr1-ligand-1-1-bis-3-indolyl-1-p-chlorophenyl-methane-modulates-glial-reactivity-and-is-neuroprotective-in-mptp-induced-parkinsonism
#6
Sean L Hammond, Katriana A Popichak, Xi Li, Lindsay G Hunt, Evan H Richman, Pranav Damale, Edwin Chong, Donald S Backos, Stephen Safe, Ronald B Tjalkens
The orphan nuclear receptor, Nurr1 (NR4A2), regulates inflammatory gene expression in glial cells, as well as genes associated with homeostatic and trophic function in dopaminergic neurons. Despite these known functions of Nurr1, an endogenous ligand has not been discovered. We postulated that activation of Nurr1 would suppress activation of glia and thereby protect against loss of dopamine (DA) neurons following subacute lesioning with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our previous studies have shown that a synthetic Nurr1 ligand, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane (C-DIM12), suppresses inflammatory gene expression in primary astrocytes and induces a dopaminergic phenotype in neurons...
April 6, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29625570/the-inhibition-of-human-lung-fibroblast-proliferation-and-differentiation-by-gs-coupled-receptors-is-not-predicted-by-the-magnitude-of-camp-response
#7
Maxine J Roberts, Rebecca E Broome, Toby C Kent, Steven J Charlton, Elizabeth M Rosethorne
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3', 5' cyclic adenosine monophosphate (cAMP) pathway is an important modulator in the development of fibrosis, with increasing levels of cAMP able to inhibit cellular processes associated with IPF...
April 7, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29625424/mglu-receptors-in-the-treatment-of-parkinson-s-disease-and-l-dopa-induced-dyskinesia
#8
REVIEW
Irene Sebastianutto, Maria Angela Cenci
Parkinson's disease (PD) is a neurodegenerative disorder characterized by typical motor features that result from dopamine (DA) depletion in the striatum. DA replacement therapy with L-DOPA is the most efficacious symptomatic treatment, but causes complications that limit its utility, in particular, L-DOPA-induced dyskinesia (LID). LID is primarily caused by pre-synaptic and post-synaptic changes in DA neurotransmission, although it also depends on altered glutamatergic transmission at several nodes of the cortico-basal ganglia-thalamocortical network...
April 3, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29619030/dopaminergic-stimulation-of-myeloid-antigen-presenting-cells-attenuates-signal-transducer-and-activator-of-transcription-3-activation-favouring-the-development-of-experimental-autoimmune-encephalomyelitis
#9
Carolina Prado, Michela Gaiazzi, Hugo González, Valentina Ugalde, Alicia Figueroa, Francisco J Osorio-Barrios, Ernesto López, Alvaro Lladser, Emanuela Rasini, Franca Marino, Mauro Zaffaroni, Marco Cosentino, Rodrigo Pacheco
The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29618432/effects-of-single-administration-of-apomorphine-on-memory-and-monoamine-metabolism-a-dose-related-study
#10
Huma Ikram, Rumaisa Zakir, Darakhshan Jabeen Haleem
In the present study, we have monitored dose dependent effects of apomorphine on learning and memory. Behavioral sensitization and craving, which develop upon repeated treatment with dopamine receptor agonist apomorphine, are major limitations of the therapeutic use of apomorphine in Parkinson's patients. Effects of single (intraperitoneal) injection of apomorphine at different doses (i.e., 0.5, 1.0, & 2.0 mg/ml/kg) on locomotion in a familiar environment (Skinner's box) and memory in Morris water maze were investigated...
March 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29615922/sensory-processing-and-integration-at-the-carotid-body-tripartite-synapse-neurotransmitter-functions-and-effects-of-chronic-hypoxia
#11
REVIEW
Erin M Leonard, Shaima Salman, Colin A Nurse
Maintenance of homeostasis in the respiratory and cardiovascular systems depends on reflexes that are initiated at specialized peripheral chemoreceptors that sense changes in the chemical composition of arterial blood. In mammals, the bilaterally-paired carotid bodies (CBs) are the main peripheral chemoreceptor organs that are richly vascularized and are strategically located at the carotid bifurcation. The CBs contribute to the maintenance of O2 , CO2 /H+ , and glucose homeostasis and have attracted much clinical interest because hyperactivity in these organs is associated with several pathophysiological conditions including sleep apnea, obstructive lung disease, heart failure, hypertension, and diabetes...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29615894/trpc1-deletion-causes-striatal-neuronal-cell-apoptosis-and-proteomic-alterations-in-mice
#12
Dian Wang, Haitao Yu, Benhong Xu, Hua Xu, Zaijun Zhang, Xiaohu Ren, Jianhui Yuan, Jianjun Liu, Yi Guo, Peter S Spencer, Xifei Yang
Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1-/- ) mice compared to that of wild type (WT) mice...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29615863/the-d2-dopamine-receptor-interferes-with-the-protective-effect-of-the-a-2a-adenosine-receptor-on-tdp-43-mislocalization-in-experimental-models-of-motor-neuron-degeneration
#13
Chia-You Lai, Yu-Ju Liu, Hsing-Lin Lai, Hui-Mei Chen, Hung-Chi Kuo, Yu-Ping Liao, Yijuang Chern
The A2A adenosine receptor (A2A R) and D2 dopamine receptor (D2 R) are two G-protein-coupled receptors that can form dimers and negatively regulate their partners. TAR DNA-binding protein (TDP-43) is a nuclear protein that has been implicated in amyotrophic lateral sclerosis (ALS). Mislocalization of TDP-43 from the nucleus to the cytoplasm is an early step of TDP-43 proteinopathy. Our previous studies indicated that A2A R is a potential drug target for ALS because treatment with an A2A R agonist (JMF1907; a T1-11 analog) prevents reactive oxygen species (ROS)-induced TDP-43 mislocalization in a motor neuron cell line (NSC34) and delays motor impairment in a TDP-43 transgenic ALS mouse model...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29614490/in-utero-exposure-to-fine-particulate-matter-causes-hypertension-due-to-impaired-renal-dopamine-d1-receptor-in-offspring
#14
Zhengmeng Ye, Xi Lu, Yi Deng, Xinquan Wang, Shuo Zheng, Hongmei Ren, Miao Zhang, Tingting Chen, Pedro A Jose, Jian Yang, Chunyu Zeng
BACKGROUND/AIMS: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2...
March 21, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29607005/the-antipsychotic-landscape-dopamine-and-beyond
#15
REVIEW
Paul D Morrison, Robin M Murray
Until recently, the actions of antipsychotic and pro-psychotic drugs have largely been evaluated in the framework of neuronal doctrine - namely, that neurons communicate by releasing transmitters, and that psychiatric disorders are caused by neurotransmitter imbalances. Moreover, the majority of studies have focused on single transmitter systems - neglecting the fact that in the nervous system, different transmitter systems work in concert and impact on not only their immediate receptors but also downstream pathways that shape structural plasticity...
April 2018: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/29606146/the-dopamine-d-1-receptor-is-expressed-and-induces-creb-phosphorylation-and-muc5ac-expression-in-human-airway-epithelium
#16
Nao Matsuyama, Sumire Shibata, Atsuko Matoba, Tada-Aki Kudo, Jennifer Danielsson, Atsushi Kohjitani, Eiji Masaki, Charles W Emala, Kentaro Mizuta
No abstract text is available yet for this article.
April 2, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29603470/a-silent-eligibility-trace-enables-dopamine-dependent-synaptic-plasticity-for-reinforcement-learning-in-the-mouse-striatum
#17
Tomomi Shindou, Mayumi Shindou, Sakurako Watanabe, Jeffery Wickens
Dopamine dependent synaptic plasticity is a candidate mechanism for reinforcement learning. A silent eligibility trace - initiated by synaptic activity and transformed into synaptic strengthening by later action of dopamine - has been hypothesized to explain the retroactive effect of dopamine in reinforcing past behaviour. We tested this hypothesis by measuring time-dependent modulation of synaptic plasticity by dopamine in adult mouse striatum, using whole-cell recordings. Presynaptic activity followed by postsynaptic action potentials (pre-post) caused spike-time dependent long-term depression in D1-expressing neurons, but not in D2 neurons, and not if postsynaptic activity followed presynaptic activity...
March 30, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29602186/molecular-mechanisms-underlying-striatal-synaptic-plasticity-relevance-to-chronic-alcohol-consumption-and-seeking
#18
Kim T Blackwell, Armando G Salinas, Parul Tewatia, Brad English, Jeanette Hellgren Kotaleski, David M Lovinger
The striatum, the input structure of the basal ganglia, is a major site of learning and memory for goal-directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and nigral inputs to learn associations, with cortico-striatal synaptic plasticity as a learning mechanism. Signaling molecules implicated in synaptic plasticity are altered in alcohol withdrawal, which may contribute to overly strong learning and increased alcohol seeking and consumption. To understand how interactions among signaling molecules produce synaptic plasticity, we implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate...
March 30, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29601869/d-serine-administration-affects-nitric-oxide-synthase-1-adaptor-protein-and-disc1-expression-in-sex-specific-manner
#19
Kirsten C Svane, Ericka-Kate Asis, Anton Omelchenko, Ansley J Kunnath, Linda M Brzustowicz, Steven M Silverstein, Bonnie L Firestein
Antipsychotic medications are inefficient at treating symptoms of schizophrenia (SCZ), and N-methyl d-aspartate receptor (NMDAR) agonists are potential therapeutic alternatives. As such, these agonists may act on different pathways and proteins altered in the brains of patients with SCZ than do antipsychotic medications. Here, we investigate the effects of administration of the antipsychotic haloperidol and NMDAR agonist d-serine on function and expression of three proteins that play significant roles in SCZ: nitric oxide synthase 1 adaptor protein (NOS1AP), dopamine D2 (D2) receptor, and disrupted in schizophrenia 1 (DISC1)...
March 27, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29599771/fresh-evidence-for-platelets-as-neuronal-and-innate-immune-cells-their-role-in-the-activation-differentiation-and-deactivation-of-th1-th17-and-tregs-during-tissue-inflammation
#20
REVIEW
Eugene D Ponomarev
Recent studies suggest that in addition to their common function in the regulation of thrombosis and hemostasis, platelets also contribute to tissue inflammation affecting adaptive immunity. Platelets have a number of pro-inflammatory and regulatory mediators stored in their α-granules and dense granules, which are promptly released at sites of inflammation or tissue injury. Platelet-derived mediators include cytokines (IL-1α, IL-1β, and TGFβ1), chemokines (CXCL4 and CCL3), immunomodulatory neurotransmitters (serotonin, dopamine, epinephrine, histamine, and GABA), and other low-molecular-weight mediators...
2018: Frontiers in Immunology
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