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Central 5-HT neurotransmission modulates weight loss following gastric bypass surgery in obese individuals.

https://arctichealth.org/en/permalink/ahliterature263720
Source
J Neurosci. 2015 Apr 8;35(14):5884-9
Publication Type
Article
Date
Apr-8-2015
Author
M E Haahr
D L Hansen
P M Fisher
C. Svarer
D S Stenbæk
K. Madsen
J. Madsen
J J Holst
W F C Baaré
L. Hojgaard
T. Almdal
G M Knudsen
Source
J Neurosci. 2015 Apr 8;35(14):5884-9
Date
Apr-8-2015
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Brain - pathology - radionuclide imaging
Brain Mapping
Case-Control Studies
Denmark
Female
Gastric Bypass - methods
Glucagon-Like Peptide 1 - blood
Humans
Ketanserin - analogs & derivatives - pharmacokinetics
Male
Middle Aged
Obesity - blood - radionuclide imaging - surgery
Protein Binding - drug effects
Receptor, Serotonin, 5-HT2A - metabolism
Serotonin Antagonists - pharmacokinetics
Time Factors
Treatment Outcome
Weight Loss - physiology
Abstract
The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB.
PubMed ID
25855196 View in PubMed
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Erythropoietin prevents secondary brain injury induced by cortical lesion in mice: possible involvement of Nrf2 signaling pathway.

https://arctichealth.org/en/permalink/ahliterature101077
Source
Ann Clin Lab Sci. 2011;41(1):25-32
Publication Type
Article
Date
2011
Author
Wei Jin
Jie Kong
Tianyu Lu
Handong Wang
Hongbin Ni
Jun Wu
Yuxiang Dai
Jian Jiang
Weibang Liang
Author Affiliation
Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
Source
Ann Clin Lab Sci. 2011;41(1):25-32
Date
2011
Language
English
Publication Type
Article
Keywords
Animals
Apoptosis - drug effects
Brain Edema - complications - pathology - physiopathology
Brain Injuries - complications - drug therapy - pathology - prevention & control
Cerebral Cortex - drug effects - enzymology - pathology - physiopathology
DNA - metabolism
Erythropoietin, Recombinant - administration & dosage - pharmacology - therapeutic use
Hand Strength - physiology
Humans
In Situ Nick-End Labeling
Male
Mice
NAD(P)H Dehydrogenase (Quinone) - genetics - metabolism
NF-E2-Related Factor 2 - genetics - metabolism
Nervous System Diseases - complications - pathology - physiopathology
Protein Binding - drug effects
RNA, Messenger - genetics - metabolism
Signal Transduction - drug effects
Abstract
Erythropoietin (EPO) has demonstrated neuroprotective effects against traumatic brain injury (TBI), but the underlying mechanisms remain unclear. The signaling pathway of an antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), has been shown in our previous studies to play an important role in protecting mice from TBI-induced secondary brain injury. The present study explored the effect of recombinant human erythropoietin (rhEPO) on cerebral activation of the Nrf2 signaling pathway and secondary brain injury in mice after TBI. Adult male ICR mice were randomly divided into three groups: (1) Sham group; (2) TBI group; and (3) TBI+rhEPO group (n = 12 per group). Closed head injury was performed using Hall's weight-dropping method. rhEPO was administered at a dose of 5,000 IU/kg at 30 min after TBI. Brain samples were extracted at 24 hr after the trauma. The treatment with rhEPO markedly up-regulated the mRNA expression and activities of Nrf2 and its downstream cytoprotective enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1). Administration of rhEPO also significantly ameliorated the secondary brain injury, as shown by decreased severity of neurological deficit, brain edema, and cortical apoptosis. In summary, post-TBI rhEPO administration induces Nrf2-mediated cytoprotective responses in the injured brain, and this may be a mechanism whereby rhEPO improves the outcome following TBI.
PubMed ID
21325251 View in PubMed
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FOXA transcription factors determine the amplitude of glucocorticoid induction of tyrosine aminotransferase in mice.

https://arctichealth.org/en/permalink/ahliterature92613
Source
Bull Exp Biol Med. 2007 Nov;144(5):722-4
Publication Type
Article
Date
Nov-2007
Author
Bryzgalov L O
Ershov N I
Ilnitskaya S I
Author Affiliation
Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk. leon_l@ngs.ru
Source
Bull Exp Biol Med. 2007 Nov;144(5):722-4
Date
Nov-2007
Language
English
Publication Type
Article
Keywords
Animals
Enzyme Activation - drug effects
Forkhead Transcription Factors - metabolism
Glucocorticoids - pharmacology
Liver - drug effects - metabolism - pathology
Liver Neoplasms - chemically induced - metabolism
Methyldimethylaminoazobenzene
Mice
Mice, Inbred ICR
Protein Binding - drug effects
Time Factors
Tyrosine Transaminase - metabolism
o-Aminoazotoluene
Abstract
o-Aminoazotoluene was more potent than 3'-methyl-4-dimethylaminoazobenzene in modulating glucocorticoid induction of tyrosine aminotransferase and DNA-binding activity of FOXA (HNF3) in 12-day-old ICR mice. In adult animals, induction of tyrosine aminotransferase and FOXA activity were modulated by o-aminoazotoluene, while 3'-methyl-4-dimethylaminoazobenzene was ineffective. Our results suggest that FOXA proteins determine glucocorticoid induction of tyrosine aminotransferase in mice (similarly to rats).
PubMed ID
18683506 View in PubMed
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Impaired maze performance in aged rats is accompanied by increased density of NMDA, 5-HT1A, and alpha-adrenoceptor binding in hippocampus.

https://arctichealth.org/en/permalink/ahliterature79778
Source
Hippocampus. 2007;17(1):68-77
Publication Type
Article
Date
2007
Author
Topic B.
Willuhn I.
Palomero-Gallagher N.
Zilles K.
Huston J P
Hasenöhrl R U
Author Affiliation
Institute of Physiological Psychology, University of Düsseldorf, Düsseldorf, Germany.
Source
Hippocampus. 2007;17(1):68-77
Date
2007
Language
English
Publication Type
Article
Keywords
Adrenergic Agents - pharmacokinetics
Aging - physiology
Animals
Behavior, Animal - physiology
Dizocilpine Maleate - pharmacokinetics
Excitatory Amino Acid Agonists - pharmacokinetics
Excitatory Amino Acid Antagonists - pharmacokinetics
Hippocampus - metabolism
Male
Maze Learning - physiology
Protein Binding - drug effects - physiology
Radioligand Assay - methods
Rats
Rats, Inbred F344
Receptor, Serotonin, 5-HT1A - metabolism
Receptors, Adrenergic, alpha - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Serotonin Agents - pharmacokinetics
Statistics, nonparametric
Tritium - pharmacokinetics
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacokinetics
Abstract
Using quantitative receptor autoradiography, we assessed binding site densities and distribution patterns of glutamate, GABA(A), acetylcholine (ACh), and monoamine receptors in the hippocampus of 32-month-old Fischer 344/Brown Norway rats. Prior to autoradiography, the rats were divided into two groups according to their retention performance in a water maze reference memory task, which was assessed 1 week after 8 days of daily maze training. The animals of the inferior group showed less long-term retention of the hidden-platform task but did not differ from superior rats in their navigation performance during place training and cued trials. The decreased retention performance in the group of inferior learners was primarily accompanied by increased alpha(1)-adrenoceptors in all hippocampal subregions under inspection (CA1-CA4 and dentate gyrus), while elevated alpha(2)-adrenoceptor binding was observed in the CA1 region and DG. Furthermore, inferior learners had higher NMDA binding in the CA2 and CA4 and increased 5-HT(1A) binding sites in the CA2, CA3, and CA4 region. No significant differences between inferior and superior learners were evident with regard to AMPA, kainate, GABA(A), muscarinergic M(1), dopamine D(1), and 5-HT(2) binding densities in any hippocampal region analyzed. These results show that increased NMDA, 5-HT(1A), and alpha-adrenoceptor binding in the hippocampus is associated with a decline in spatial memory. The increased receptor binding observed in the group of old rats with inferior maze performance might be the result of neural adaptation triggered by age-related changes in synaptic connectivity and/or synaptic activity.
PubMed ID
17111411 View in PubMed
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Oligomer-targeting with a conformational antibody fragment promotes toxicity in Aß-expressing flies.

https://arctichealth.org/en/permalink/ahliterature258886
Source
Acta Neuropathol Commun. 2014;2:43
Publication Type
Article
Date
2014
Author
Jessica Wacker
Raik Rönicke
Martin Westermann
Melanie Wulff
Klaus G Reymann
Christopher M Dobson
Uwe Horn
Damian C Crowther
Leila M Luheshi
Marcus Fändrich
Source
Acta Neuropathol Commun. 2014;2:43
Date
2014
Language
English
Publication Type
Article
Keywords
Amino Acid Sequence
Amyloid beta-Peptides - genetics - immunology - metabolism - pharmacology
Animals
Animals, Genetically Modified
Antibodies - chemistry - genetics - pharmacology - therapeutic use
Cell Line, Tumor
Disease Models, Animal
Drosophila Proteins - genetics
Drosophila melanogaster
Eye - metabolism - ultrastructure
Hippocampus - drug effects - physiology
Humans
Long-Term Potentiation - drug effects - genetics
Mice
Mice, Inbred C57BL
Neuroblastoma - pathology
Neurotoxicity Syndromes - drug therapy - etiology - physiopathology
Peptide Fragments - genetics - immunology - metabolism - pharmacology
Protein Aggregation, Pathological
Protein Binding - drug effects
Protein Conformation
Abstract
The self-assembly of Aß peptides into a range of conformationally heterogeneous amyloid states represents a fundamental event in Alzheimer's disease. Within these structures oligomeric intermediates are considered to be particularly pathogenic. To test this hypothesis we have used a conformational targeting approach where particular conformational states, such as oligomers or fibrils, are recognized in vivo by state-specific antibody fragments.
We show that oligomer targeting with the KW1 antibody fragment, but not fibril targeting with the B10 antibody fragment, affects toxicity in Aß-expressing Drosophila melanogaster. The effect of KW1 is observed to occur selectively with flies expressing Aß(1-40) and not with those expressing Aß(1-42) or the arctic variant of Aß(1-42) This finding is consistent with the binding preference of KW1 for Aß(1-40) oligomers that has been established in vitro. Strikingly, and in contrast to the previously demonstrated in vitro ability of this antibody fragment to block oligomeric toxicity in long-term potentiation measurements, KW1 promotes toxicity in the flies rather than preventing it. This result shows the crucial importance of the environment in determining the influence of antibody binding on the nature and consequences of the protein misfolding and aggregation.
While our data support to the pathological relevance of oligomers, they highlight the issues to be addressed when developing inhibitory strategies that aim to neutralize these states by means of antagonistic binding agents.
Notes
Cites: Prog Mol Biol Transl Sci. 2012;107:101-2422482449
Cites: Nat Med. 2008 Oct;14(10):1106-1118836460
Cites: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11172-722745165
Cites: J Mol Biol. 2012 Aug 24;421(4-5):427-4022248587
Cites: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12503-822814377
Cites: Genetics. 2000 Nov;156(3):1117-2711063688
Cites: Science. 2001 Jul 27;293(5530):711-411408621
Cites: Nat Neurosci. 2001 Sep;4(9):887-9311528419
Cites: J Neurochem. 2001 Nov;79(3):595-60511701763
Cites: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1485-9011818542
Cites: Science. 2003 Apr 18;300(5618):486-912702875
Cites: Lancet Neurol. 2003 Apr;2(4):215-2012849209
Cites: N Engl J Med. 2003 Aug 7;349(6):583-9612904524
Cites: Trends Biochem Sci. 2004 Oct;29(10):542-715450609
Cites: Anal Biochem. 1989 Nov 1;182(2):319-262610349
Cites: Development. 1993 Jun;118(2):401-158223268
Cites: Neuroscience. 2005;132(1):123-3515780472
Cites: Protein Sci. 2005 Jul;14(7):1753-915937275
Cites: Protein Sci. 2005 Aug;14(8):2125-3115987892
Cites: J Biol Chem. 2006 Feb 17;281(7):4292-916361260
Cites: Nature. 2006 Mar 16;440(7082):352-716541076
Cites: Annu Rev Biochem. 2006;75:333-6616756495
Cites: Q Rev Biophys. 2006 May;39(2):167-20116978447
Cites: Nat Rev Mol Cell Biol. 2007 Feb;8(2):101-1217245412
Cites: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3312-717360644
Cites: PLoS Biol. 2007 Oct 30;5(11):e29017973577
Cites: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19232-718042730
Cites: FEBS Lett. 2009 Feb 4;583(3):579-8419162022
Cites: PLoS One. 2009;4(5):e572719492089
Cites: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9191-619458258
Cites: Eur J Neurosci. 2009 Apr;29(7):1335-4719519625
Cites: Neurobiol Aging. 2010 Feb;31(2):189-20218486276
Cites: PLoS Biol. 2010 Mar;8(3):e100033420305716
Cites: J Neurosci. 2010 Aug 4;30(31):10369-7920685980
Cites: ACS Chem Biol. 2010 Aug 20;5(8):735-4020550130
Cites: PLoS Genet. 2010 Sep;6(9):e100108720824130
Cites: Annu Rev Cell Dev Biol. 2010;26:211-3320500090
Cites: PLoS One. 2010;5(10):e1339120967130
Cites: J Mol Biol. 2011 Jan 14;405(2):341-821059358
Cites: Nat Rev Neurosci. 2011 Feb;12(2):65-7221193853
Cites: J Biol Chem. 2011 Feb 11;286(6):4248-5621147772
Cites: Angew Chem Int Ed Engl. 2011 Mar 14;50(12):2837-4021387500
Cites: J Mol Biol. 2011 May 6;408(3):529-4021376731
Cites: Amyloid. 2011 Jun;18(2):47-5221401323
Cites: Mol Cell. 2011 Jul 8;43(1):8-1821726806
Cites: J Cell Mol Med. 2012 Feb;16(2):287-9521418518
Cites: Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):84-922171009
Cites: Neurobiol Aging. 2011 Dec;32(12):2219-2820133015
Cites: Angew Chem Int Ed Engl. 2012 Feb 13;51(7):1576-922234970
Cites: Cell. 2012 Mar 16;148(6):1188-20322424229
Cites: EMBO J. 2008 Jan 9;27(1):224-3318059472
Cites: Angew Chem Int Ed Engl. 2008;47(22):4062-918412209
Cites: PLoS One. 2008;3(9):e323618800168
Cites: J Biol Chem. 2012 Jun 8;287(24):20748-5422461632
PubMed ID
24725347 View in PubMed
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Synthesis and HIV-1 integrase inhibitory activity of spiroundecane(ene) derivatives.

https://arctichealth.org/en/permalink/ahliterature79308
Source
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1362-8
Publication Type
Article
Date
Mar-1-2007
Author
Shults Elvira E
Semenova Elena A
Johnson Allison A
Bondarenko Svetlana P
Bagryanskaya Irina Y
Gatilov Yuri V
Tolstikov Genrikh A
Pommier Yves
Author Affiliation
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation. schultz@nioch.nsc.ru
Source
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1362-8
Date
Mar-1-2007
Language
English
Publication Type
Article
Keywords
Alkanes - chemical synthesis - pharmacology
Anti-HIV Agents - chemical synthesis
Catalysis - drug effects
Crystallography, X-Ray
HIV Integrase - drug effects
HIV Integrase Inhibitors - chemical synthesis - chemistry - pharmacology
Humans
Inhibitory Concentration 50
Protein Binding - drug effects
Spiro Compounds - chemical synthesis - pharmacology
Structure-Activity Relationship
Abstract
Fifteen 2,4-dioxaspiro[5.5]undecane ketone and 2,4-dioxa-spiro[5.5]undec-8-ene (spiroundecane(ene)) derivatives were synthesized using the Diels-Alder reaction. Inhibition of human immunodeficiency virus integrase (IN) was examined. Eight spiroundecane(ene) derivatives inhibited both 3'-processing and strand transfer reactions catalyzed by IN. SAR studies showed that the undecane core with at least one furan moiety is preferred for IN inhibition. Moreover, crosslinking experiments showed that spiroundecane derivatives did not affect IN-DNA binding at concentrations that block IN catalytic activity, indicating spiroundecane derivatives inhibit preformed IN-DNA complex. The moderate toxicity of spiroundecane(ene) derivatives encourages the further design of therapeutically relevant analogues based on this novel chemotype of IN inhibitors.
PubMed ID
17189685 View in PubMed
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[Transformation of specific antibodies to polyreactive immunoglobulins and their binding to blood vessel walls]

https://arctichealth.org/en/permalink/ahliterature9669
Source
Ukr Biokhim Zh. 2002 May-Jun;74(3):133-41
Publication Type
Article
Author
S A Bobrovnik
Author Affiliation
Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv. sab@biochem.kiev.ua
Source
Ukr Biokhim Zh. 2002 May-Jun;74(3):133-41
Language
Russian
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - drug effects - metabolism
Antibody Specificity - drug effects
Antigen-Antibody Reactions
Blood Vessels - drug effects - metabolism
Dimethyl Sulfoxide - administration & dosage - pharmacology
Edetic Acid - administration & dosage - metabolism
English Abstract
Ethanol - administration & dosage - pharmacology
Immunoglobulins - blood - immunology
In Vitro
Injections, Intravenous
Mice
Mice, Inbred C57BL
Muscle, Skeletal - blood supply - drug effects - metabolism
Protein Binding - drug effects
Abstract
It was shown that 30-50% ethanol or 40-70% dimetilsulfoxide could efficiently induce in vitro transformation of specific monoclonal antibodies (mAbs) into non-specific polyreactive immunoglobulins (PRIG). Intravenous injection 0.4 ml of FeSO4-EDTA mixture (60 and 30 mkM respectively) could induce increase of PRIG reactivity in the blood-stream. Intramuscle injection of either 0.1 ml of 40% ethanol, or 0.1 ml of FeSO4-EDTA mixture into muscle of hind limb of C57B1 mice leads to the substantial binding of circulated immunoglobulins to the blood vessels of the muscle. The similar effect could also be induced by ischemia/reperfusion of mice hind limb. In the case of intravenous injection of specific to ovalbumin biotinilated mAbs, the subsequent intramuscle injection of 0.1 ml of 40% ethanol induces apparent transformation of these mAbs into PRIG and their binding to the blood vessels. Intramuscle injection of 0.1 ml of FeSO4-EDTA mixture induces less than ethanol though noticeable effect. The obtained data have shown that cord-blood circulating specific antibodies could be transformed into PRIG at some conditions in vivo. If so, this process might play an important role in the organism defence against infections but could, probably, facilitate the development of atherosclerosis, cardiac infarct, cerebral stroke or tumors.
PubMed ID
12916252 View in PubMed
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7 records – page 1 of 1.