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https://www.readbyqxmd.com/read/27930324/dopamine-release-from-the-locus-coeruleus-to-the-dorsal-hippocampus-promotes-spatial-learning-and-memory
#1
Kimberly A Kempadoo, Eugene V Mosharov, Se Joon Choi, David Sulzer, Eric R Kandel
Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC)...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27825624/quantification-of-suvorexant-in-urine-using-gas-chromatography-mass-spectrometry
#2
Mariah Carson, Sarah Kerrigan
Suvorexant (Belsomra(®)) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs). Sedative hypnotics with central nervous system depressant effects feature prominently in forensic toxicology investigations. For this reason, a new analytical method was developed to identify suvorexant in urine using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS)...
November 2, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27817026/the-inhibition-of-dopamine-synthesis-in-fetuses-changes-the-pattern-of-t-lymphocyte-maturation-in-the-thymus-of-adult-rats
#3
N V Lifantseva, Ts O Koneeva, S N Voronova, L A Zakharova, V I Melnikova
The mRNA for dopamine receptors of type D1, D3, D5, but not type D2, was detected in the thymus of rats starting from day 16 of embryonic development (E16). Dopamine at concentrations of 10(-8)-10(‒6) M inhibited fetus thymocyte response to mitogen, confirming the functionality of the receptors and the possibility of a direct effect of dopamine on the developing thymus. Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes...
September 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27811173/an-allosteric-potentiator-of-the-dopamine-d1-receptor-increases-locomotor-activity-in-human-d1-knock-in-mice-without-causing-stereotypy-or-tachyphylaxis
#4
Kjell A Svensson, Beverly A Heinz, John M Schaus, James P Beck, Junliang Hao, Joseph H Krushinski, Matthew R Reinhard, Michael P Cohen, Sarah L Hellman, Brian G Getman, Xushan Wang, Michelle M Menezes, Deanna L Maren, Julie F Falcone, Wesley H Anderson, Rebecca A Wright, S Michelle Morin, Kelly L Knopp, Benjamin L Adams, Borys Rogovoy, Ilya Okun, Todd M Suter, Michael A Statnick, Donald R Gehlert, David L Nelson, Virginia L Lucaites, Renee Emkey, Neil W DeLapp, Todd R Wiernicki, Jeffrey W Cramer, Charles R Yang, Robert F Bruns
Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor potentiator DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one]. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a Kb of 26 nM...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27793671/antiferroptotic-activity-of-non-oxidative-dopamine
#5
Ding Wang, Yingpeng Peng, Yangchun Xie, Borong Zhou, Xiaofang Sun, Rui Kang, Daolin Tang
Dopamine is a neurotransmitter that has many functions in the nervous and immune systems. Ferroptosis is a non-apoptotic form of regulated cell death that is involved in cancer and neurodegenerative diseases. However, the role of dopamine in ferroptosis remains unidentified. Here, we show that the non-oxidative form of dopamine is a strong inhibitor of ferroptotic cell death. Dopamine dose-dependently blocked ferroptosis in cancer (PANC1 and HEY) and non-cancer (MEF and HEK293) cells following treatment with erastin, a small molecule ferroptosis inducer...
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27725799/loss-of-catecholaminergic-neuromodulation-of-persistent-forms-of-hippocampal-synaptic-plasticity-with-increasing-age
#6
Hannah Twarkowski, Denise Manahan-Vaughan
Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24 h), and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP) and long-term depression (LTD), but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27721791/dopamine-d1-d5-but-not-d2-d3-receptor-dependency-of-synaptic-plasticity-at-hippocampal-mossy-fiber-synapses-that-is-enabled-by-patterned-afferent-stimulation-or-spatial-learning
#7
Hardy Hagena, Denise Manahan-Vaughan
Although the mossy fiber (MF) synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24 h) synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH)-CA1 and perforant path (PP)-dentate gyrus (DG) synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP) and long-term depression (LTD)...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27609280/dopaminergic-receptors-and-adrenoceptors-in-circulating-lymphocytes-as-putative-biomarkers-for-the-early-onset-and-progression-of-multiple-sclerosis
#8
Marco Cosentino, Mauro Zaffaroni, Massimiliano Legnaro, Raffaella Bombelli, Laura Schembri, Damiano Baroncini, Anna Bianchi, Raffaella Clerici, Mario Guidotti, Paola Banfi, Giorgio Bono, Franca Marino
Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients...
September 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27602521/locus-coeruleus-and-dopaminergic-consolidation-of-everyday-memory
#9
Tomonori Takeuchi, Adrian J Duszkiewicz, Alex Sonneborn, Patrick A Spooner, Miwako Yamasaki, Masahiko Watanabe, Caroline C Smith, Guillén Fernández, Karl Deisseroth, Robert W Greene, Richard G M Morris
The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH(+)) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH(+) neurons project more profusely than ventral tegmental area TH(+) neurons to the hippocampus, optogenetic activation of locus coeruleus TH(+) neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation...
September 7, 2016: Nature
https://www.readbyqxmd.com/read/27597526/validation-of-an-improved-scale-for-rating-l-dopa-induced-dyskinesia-in-the-mouse-and-effects-of-specific-dopamine-receptor-antagonists
#10
Irene Sebastianutto, Natallia Maslava, Corey R Hopkins, M Angela Cenci
Rodent models of l-DOPA-induced dyskinesia (LID) are essential to investigate pathophysiological mechanisms and treatment options. Ratings of abnormal involuntary movements (AIMs) are used to capture both qualitative and quantitative features of dyskinetic behaviors. Thus far, validated rating scales for the mouse have anchored the definition of severity to the time during which AIMs are present. Here we have asked whether the severity of axial, limb, and orolingual AIMs can be objectively assessed with scores based on movement amplitude...
September 2, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27541930/modulation-of-dopaminergic-pathways-to-treat-erectile-dysfunction
#11
Ulf Simonsen, Simon Comerma-Steffensen, Karl-Erik Andersson
The currently recommended first-line treatments of erectile dysfunction, phosphodiesterase type 5 inhibitors (PDE5i), e.g. sildenafil, are efficacious in many patients with erectile dysfunction of vascular origin, but this therapy is insufficient in approximately 30-40% of men with erectile dysfunction where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )-and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial preoptic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for treatment of Parkinson's disease are associated with increased libido...
August 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27533478/3-dicyanomethylidene-indan-1-one-functionalized-calix-4-arene-calix-4-pyrrole-hybrid-an-ion-pair-sensor-for-cesium-salts
#12
Yerim Yeon, Soojung Leem, Corin Wagen, Vincent M Lynch, Sung Kuk Kim, Jonathan L Sessler
A chromogenic calix[4]arene-calix[4]pyrrole hybrid ion pair receptor bearing an indane substituent at a β-pyrrolic position has been prepared. On the basis of solution-phase UV-vis spectroscopic analysis and (1)H NMR spectroscopic studies carried out in 10% methanol in chloroform, receptor 1 is able to bind only cesium ion pairs (e.g., CsF, CsCl, and CsNO3) but not the constituent cesium cation (as its perchlorate salt) or the F(-), Cl(-), or NO3(-) anions (as the tetrabutylammonium salts). It thus displays rudimentary AND logic gate behavior...
September 2, 2016: Organic Letters
https://www.readbyqxmd.com/read/27525724/kinetic-mrna-profiling-in-a-rat-model-of-left-ventricular-hypertrophy-reveals-early-expression-of-chemokines-and-their-receptors
#13
Simona Nemska, Laurent Monassier, Max Gassmann, Nelly Frossard, Reza Tavakoli
Left-ventricular hypertrophy (LVH), a risk factor for heart failure and death, is characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and leukocyte infiltration. Chemokines interacting with G protein-coupled chemokine receptors may play a role in LVH development by promoting recruitment of activated leukocytes or modulating left-ventricular remodeling. Using a pressure overload-induced kinetic model of LVH in rats, we examined during 14 days the expression over time of chemokine and chemokine receptor mRNAs in left ventricles from aortic-banded vs sham-operated animals...
2016: PloS One
https://www.readbyqxmd.com/read/27470093/differential-involvement-of-ca-2-calmodulin-dependent-protein-kinases-and-mitogen-activated-protein-kinases-in-the-dopamine-d1-d5-receptor-mediated-potentiation-in-hippocampal-ca1-pyramidal-neurons
#14
Mahesh Shivarama Shetty, Sreedharan Sajikumar
Dopaminergic neurotransmission modulates and influences hippocampal CA1 synaptic plasticity, learning and long-term memory mechanisms. Investigating the mechanisms involved in the slow-onset potentiation induced by the dopamine D1/D5 receptor agonists in hippocampal CA1 region, we have reported recently that it could play a role in regulating synaptic cooperation and competition. We have also shown that a sustained activation of MEK/MAP kinase pathway was involved in the maintenance of this long-lasting potentiation (Shivarama Shetty, Gopinadhan, & Sajikumar, 2016)...
July 25, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27469513/effects-of-ketamine-and-ketamine-metabolites-on-evoked-striatal-dopamine-release-dopamine-receptors-and-monoamine-transporters
#15
Adem Can, Panos Zanos, Ruin Moaddel, Hye Jin Kang, Katinia S S Dossou, Irving W Wainer, Joseph F Cheer, Douglas O Frost, Xi-Ping Huang, Todd D Gould
Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine's antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine's side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system...
October 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27423521/effects-of-d1-receptor-knockout-on-fear-and-reward-learning
#16
Antony D Abraham, Kim A Neve, K Matthew Lattal
Dopamine signaling is involved in a variety of neurobiological processes that contribute to learning and memory. D1-like dopamine receptors (including D1 and D5 receptors) are thought to be involved in memory and reward processes, but pharmacological approaches have been limited in their ability to distinguish between D1 and D5 receptors. Here, we examine the effects of a specific knockout of D1 receptors in associative learning tasks involving aversive (shock) or appetitive (cocaine) unconditioned stimuli...
September 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27412418/biophysical-and-biochemical-characterization-of-avian-secretory-component-provides-structural-insights-into-the-evolution-of-the-polymeric-ig-receptor
#17
Beth M Stadtmueller, Zhongyu Yang, Kathryn E Huey-Tubman, Helena Roberts-Mataric, Wayne L Hubbell, Pamela J Bjorkman
The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27397110/preventative-treatment-in-an-animal-model-of-adhd-behavioral-and-biochemical-effects-of-methylphenidate-and-its-interactions-with-ovarian-hormones-in-female-rats
#18
Jodi L Lukkes, Nadja Freund, Britta S Thompson, Shirisha Meda, Susan L Andersen
Clinical and preclinical studies on attention deficit hyperactivity disorder (ADHD) show that juvenile males that are exposed to methylphenidate (MPH) show reduced risk for substance use later in life. In contrast, little is known about whether females have the same enduring treatment response to stimulants and how gonadal hormones influence their behavior later in life. Females received either a sham or 6-hydroxydopamine (6-OHDA) microinjection in the prefrontal cortex (PFC) at postnatal day (P)10. Subjects were then treated with Vehicle or MPH (2mg/kg, p...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27373649/efficient-n-acyldopamine-synthesis
#19
Yotaro Matsumoto, Akihiro Ito, Motonari Uesugi, Atsushi Kittaka
N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N-arachidonoyldopamine (AADA) and N-oleoyldopamine (ODA) were characterized as transient receptor potential vanilloid type V1 channel (TRPV1) ligands. Recently, it was shown that N-acyldopamines may possess diverse physiological roles in addition to their ligand activities. To study the multiple functions and action mechanisms of endogenous N-acyldopamines, a simple and efficient method of N-acyldopamine synthesis was investigated...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27320930/potential-of-specialized-pro-resolving-lipid-mediators-against-rheumatic-diseases
#20
Kosaku Murakami
  While arachidonic acid (AA), which is classified into n-6 polyunsaturated fatty acid (PUFA), has been mainly recognized as a substrate of pro-inflammatory mediators, eicosapentaenoic acid or docosahexaenoic acid, which are classified into n-3 PUFA, is currently identified as substrates of mediators inducing resolution of inflammation, namely pro-resolving mediators (SPM). As with any other pathological conditions, it is gradually elucidated that SPMs contributes a certain effect on joint inflammation. In osteoarthritis (OA), Lipid fractions extracted from adipocytes, especially in infrapatellar fat pad rather than subcutaneous tissue induce T cell skewing for producing IFN-γ or decrease the production of IL-12p40 from macrophages...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
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