当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease.

Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease.

Abstract：

BACKGROUND AND PURPOSE:Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-related behaviour were investigated. EXPERIMENTAL APPROACH:Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age-matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil. KEY RESULTS:Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperphosphorylation and a decrease in the activity of glycogen synthase kinase 3β (GSK3β) and of cyclin-dependent kinase 5 (CDK5) (p25/p35 ratio). Moreover, sildenafil also increased levels of brain-derived neurotrophic factor (BDNF) and the activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus without any detectable modification of brain amyloid burden. CONCLUSIONS AND IMPLICATIONS:Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Cuadrado-Tejedor M,Hervias I,Ricobaraza A,Puerta E,Pérez-Roldán JM,García-Barroso C,Franco R,Aguirre N,García-Osta A

doi

10.1111/j.1476-5381.2011.01517.x

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

2029-41

issue

8

eissn

0007-1188

issn

1476-5381

journal_volume

164

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF PHARMACOLOGY文献大全
  • Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat.

    abstract：:The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammato...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1982.tb08783.x

    authors： Belo SE,Talesnik J

    更新日期：1982-02-01 00:00:00

  • Factors influencing the release of acetylcholine from the myenteric plexus of the ileum of the guinea-pig and rabbit.

    abstract：:1 The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea-pig, the acetylcholi...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1978.tb17319.x

    authors： Cowie AL,Kosterlitz HW,Waterfield AA

    更新日期：1978-12-01 00:00:00

  • Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.

    abstract：:1. Glycine responses were studied under voltage clamp in Xenopus oocytes injected with cDNA encoding mammalian glycine receptor subunits and in rat medullary neurones. Bath application of glycine gave strychnine-sensitive currents which reversed close to the expected equilibrium potentials for chloride ions. The peak ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1996.tb15430.x

    authors： Downie DL,Hall AC,Lieb WR,Franks NP

    更新日期：1996-06-01 00:00:00

  • Non-specific activity of (+/-)-CP-96,345 in models of pain and inflammation.

    abstract：:The non-peptide NK1 receptor antagonist, CP-96,345, and its 2R,3R enantiomer CP-96,344, which is not an NK1 receptor antagonist (IC50 > 10 microM), were evaluated for antinociceptive and anti-inflammatory activities in several classical models of pain and inflammation in the rat. Both CP-96,345 and CP-96,344 reduced c...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1992.tb12737.x

    authors： Nagahisa A,Asai R,Kanai Y,Murase A,Tsuchiya-Nakagaki M,Nakagaki T,Shieh TC,Taniguchi K

    更新日期：1992-10-01 00:00:00

  • Distinct functions of endogenous cannabinoid system in alcohol abuse disorders.

    abstract：:Δ9 -tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB1 and CB2 receptors on the cell surface. The CB1 receptors are present in both inhibitory and excitatory presynaptic terminals and the CB2 receptors are fo...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/bph.14780

    authors： Basavarajappa BS,Joshi V,Shivakumar M,Subbanna S

    更新日期：2019-09-01 00:00:00

  • Antagonistic effect of compound 48/80 on the inhibitory actions of morphine and methionine-enkephalin on electrically-induced contractions of the guinea-pig ileum.

    abstract：:1 The effect of compound 48/80 was studied on the twitch-like contractions of the longitudinal muscle of guinea-pig ileum induced by electrical stimulation of intramural cholinergic nerves. 2 Compound 48/80 alone, at concentrations up to 30 microgram/ml, had no effect on the twitch contractions. The contraction to exo...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1978.tb17312.x

    authors： Kamikawa Y,Shimo Y

    更新日期：1978-12-01 00:00:00

  • Two distinct membrane currents activated by cyclopiazonic acid-induced calcium store depletion in single smooth muscle cells of the mouse anococcygeus.

    abstract：:1. By use of the whole-cell configuration of the patch-clamp technique, membrane currents induced by cyclopiazonic acid (CPA; an inhibitor of the sarcoplasmic reticulum (SR) calcium-ATPase) were investigated in single smooth muscle cells freshly dispersed from the mouse anococcygeus. Voltage-dependent calcium currents...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1996.tb15228.x

    authors： Wayman CP,McFadzean I,Gibson A,Tucker JF

    更新日期：1996-02-01 00:00:00

  • Neuropeptide Y2 receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats.

    abstract：:1. The present study addressed the role of neuropeptide (NPY) Y2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Wester...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0706774

    authors： Gradin KA,Buus CL,Li JY,Frøbert O,Simonsen U

    更新日期：2006-07-01 00:00:00

  • Effect of M & B 17803A, a new -adrenoceptor blocking agent, on the cardiovascular responses to tilting and to isoprenaline in man.

    abstract：:1. DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M & B 17803A) was given to four healthy volunteers in single oral doses of up to 300 mg. There were no subjective effects and no significant alterations in the heart rate, systolic and diastolic blood pressure in the seated posit...

    journal_title：British journal of pharmacology

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1111/j.1476-5381.1971.tb07193.x

    authors： Cuthbert MF,Owusu-Ankomah K

    更新日期：1971-11-01 00:00:00

  • 5-HT2B receptor-mediated calcium release from ryanodine-sensitive intracellular stores in human pulmonary artery endothelial cells.

    abstract：:1. We have characterized the 5-hydroxytryptamine (5-HT)-induced calcium signalling in endothelial cells from the human pulmonary artery. Using RT-PCR we show, that of all cloned G-protein coupled 5-HT receptors, these cells express only 5-HT1D beta, 5-HT2B and little 5-HT4 receptor mRNA. 2. In endothelial cells 5-HT i...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1996.tb16700.x

    authors： Ullmer C,Boddeke HG,Schmuck K,Lübbert H

    更新日期：1996-03-01 00:00:00

  • Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via activation of TEA-sensitive potassium channels.

    abstract：BACKGROUND AND PURPOSE:Central anti-nociceptive actions of baclofen involve activation of K+ channels. Here we assessed what types of K+ channel might participate in the peripheral anti-nociception induced by baclofen. EXPERIMENTAL APPROACH:Nociceptive thresholds to mechanical stimulation in rat paws treated with intr...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0706898

    authors： Reis GM,Duarte ID

    更新日期：2006-11-01 00:00:00

  • Characterization of protein serine/threonine phosphatase activities in human lung mast cells and basophils.

    abstract：:1. The serine/threonine protein phosphatase (PP) inhibitors, okadaic acid and calyculin, attenuated the IgE-mediated release of histamine from human lung mast cells (HLMC) and basophils in a dose-dependent manner whereas an alternative PP inhibitor, microcystin, was ineffective. Calyculin was more potent than okadaic ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0702169

    authors： Peirce MJ,Munday MR,Peachell PT

    更新日期：1998-11-01 00:00:00

  • Spasmolytic effects of cadmium and zinc ions upon the guinea-pig isolated ileum preparation.

    abstract：:1. An investigation has been made of the effects of cadmium and zinc ions upon the contractile response of the guinea-pig isolated ileum to methacholine, histamine, potassium ion and a.c. field stimulation. The metal ions depress the response to all of these agents.2. Radioisotope studies showed that cadmium and zinc ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1971.tb08046.x

    authors： Schnieden H,Small RC

    更新日期：1971-03-01 00:00:00

  • Formation of sulphidopeptide-leukotrienes by cell-cell interaction causes coronary vasoconstriction in isolated, cell-perfused heart of rabbit.

    abstract：:1. We have studied the transcellular biosynthesis of bioactive leukotrienes (LTs), generated upon blood cell-vascular wall interactions and their functional consequences, in the spontaneously beating, cell-perfused, heart of the rabbit. Rabbit isolated hearts were perfused under recirculating conditions (50 ml) with 5...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1993.tb13943.x

    authors： Sala A,Rossoni G,Buccellati C,Berti F,Folco G,Maclouf J

    更新日期：1993-11-01 00:00:00

  • Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens.

    abstract：BACKGROUND AND PURPOSE:Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.12690

    authors： Feduccia AA,Simms JA,Mill D,Yi HY,Bartlett SE

    更新日期：2014-07-01 00:00:00

  • 5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis.

    abstract：BACKGROUND AND PURPOSE:5-HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5-HT and 5-HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neuro...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/bph.13482

    authors： Utsumi D,Matsumoto K,Amagase K,Horie S,Kato S

    更新日期：2016-06-01 00:00:00

  • The structural role of receptor tyrosine sulfation in chemokine recognition.

    abstract：:Tyrosine sulfation is a post-translational modification of secreted and transmembrane proteins, including many GPCRs such as chemokine receptors. Most chemokine receptors contain several potentially sulfated tyrosine residues in their extracellular N-terminal regions, the initial binding site for chemokine ligands. Su...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1111/bph.12455

    authors： Ludeman JP,Stone MJ

    更新日期：2014-03-01 00:00:00

  • Stress-induced anhedonia is associated with an increase in Alzheimer's disease-related markers.

    abstract：BACKGROUND AND PURPOSE:Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD-related markers. EXPERIMENTAL APPROACH:Anhedonia induced by a chron...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.2011.01602.x

    authors： Briones A,Gagno S,Martisova E,Dobarro M,Aisa B,Solas M,Tordera R,Ramírez M

    更新日期：2012-02-01 00:00:00

  • The gastric H,K-ATPase blocker lansoprazole is an inhibitor of chloride channels.

    abstract：:1. It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, w...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703070

    authors： Schmarda A,Dinkhauser P,Gschwentner M,Ritter M,Fürst J,Scandella E,Wöll E,Laich A,Rossmann H,Seidler U,Lang F,Paulmichl M

    更新日期：2000-02-01 00:00:00

  • Effect of adrenergic and nitrergic blockade on experimental ileus in rats.

    abstract：:1. In a rat model of experimental ileus, the effect of blockade of adrenergic and nitrergic neurotransmission was studied on the intestinal transit of Evans blue. 2. Ether anaesthesia and skin incision had no influence on the transit. Laparotomy significantly inhibited the transit of Evans blue. This inhibition was ev...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0700913

    authors： De Winter BY,Boeckxstaens GE,De Man JG,Moreels TG,Herman AG,Pelckmans PA

    更新日期：1997-02-01 00:00:00

  • Effects of changes in the structure of enkephalins and of narcotic analgesic drugs on their interactions with mu- and delta-receptors.

    abstract：:1 The activity pattern of analogues of the enkephalins was determined in four parallel assays, the inhibition of the electrically evoked contraction of the guinea-pig ileum and mouse vas deferens at 36 degrees C and the inhibition of [(3)H]-naltrexone and [(3)H]-leucine-enkephalin binding at 0 to 4 degrees C in homoge...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1980.tb10422.x

    authors： Kosterlitz HW,Lord JA,Paterson SJ,Waterfield AA

    更新日期：1980-02-01 00:00:00

  • Effects of protein tyrosine kinase inhibitors on voltage-operated calcium channel currents in vascular smooth muscle cells and pp60(c-src) kinase activity.

    abstract：:1. Tyrosine kinases have been proposed as regulators of voltage-operated calcium channels. The effects of a range of structurally different inhibitors of protein tyrosine kinases (PTK) were examined on voltage-operated calcium channel currents (I(Ba)) and pp60(c-src) kinase (c-src) activity in vitro. 2. I(Ba) was meas...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0703186

    authors： Wijetunge S,Lymn JS,Hughes AD

    更新日期：2000-04-01 00:00:00

  • Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells.

    abstract：:We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by alpha-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages. DFMO potentiated LPS-stimulated nitrite production in both a concentration- and t...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0702231

    authors： Baydoun AR,Morgan DM

    更新日期：1998-12-01 00:00:00

  • Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular muscle cells.

    abstract：:Ryanodine (1 microM) suppressed or abolished contraction in response to step depolarization in voltage-clamped cells isolated from adult rat ventricular myocardium. The step depolarizations evoked the second inward current, which is carried largely by Ca ions under these conditions, and there was little or no change i...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1984.tb10735.x

    authors： Mitchell MR,Powell T,Terrar DA,Twist VW

    更新日期：1984-01-01 00:00:00

  • Pharmacological properties of the cloned alpha 1A/D-adrenoceptor subtype are consistent with the alpha 1A-adrenoceptor characterized in rat cerebral cortex and vas deferens.

    abstract：:1. The pharmacological characteristics of cloned mammalian alpha 1A/D-, alpha 1B- and alpha 1C-adrenoceptor subtypes expressed in rat 1 fibroblasts were determined in comparison to the binding and functional properties of these subtypes in rat tissues. 2. Analysis of [3H]-prazosin binding to membrane homogenates from ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1994.tb14843.x

    authors： Kenny BA,Naylor AM,Greengrass PM,Russell MJ,Friend SJ,Read AM,Wyllie MG

    更新日期：1994-04-01 00:00:00

  • Involvement of reactive oxygen species in cyclic stretch-induced NF-kappaB activation in human fibroblast cells.

    abstract：:1 Uniaxial cyclic stretch leads to an upregulation of cyclooxygenase (COX)-2 through increases in the intracellular Ca(2+) concentration via the stretch-activated (SA) channel and following nuclear factor kappa B (NF-kappaB) activation in human fibroblasts. However, the signaling mechanism as to how the elevated Ca(2+...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0706182

    authors： Amma H,Naruse K,Ishiguro N,Sokabe M

    更新日期：2005-06-01 00:00:00

  • Inhibition of slow Ca(2+)-activated K(+) current by 4-aminopyridine in rat hippocampal CA1 pyramidal neurones.

    abstract：:1. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing cur...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1038/sj.bjp.0704533

    authors： Andreasen M

    更新日期：2002-02-01 00:00:00

  • Benzodiazepine-induced intestinal motor disturbances in rats: mediation by omega 2 (BZ2) sites on capsaicin-sensitive afferent neurones.

    abstract：:1. The central and peripheral effects of the omega (benzodiazepine) site ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on intestinal myoelectrical activity were evaluated in conscious rats, chronically f...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1994.tb16204.x

    authors： Bonnafous C,Scatton B,Buéno L

    更新日期：1994-09-01 00:00:00

  • Antithrombotic actions of the thrombin inhibitor, argatroban, in a canine model of coronary cyclic flow: comparison with heparin.

    abstract：:1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in a canine model of coronary cyclic flow having some of the characteristics of acute unstable angina. Heparin was studied as a reference anticoagulant. 2. Localized endothelial damage was induced in the circumflex coronary artery ...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1996.tb15460.x

    authors： Duval N,Lunven C,O'Brien DP,Grosset A,O'Connor SE,Berry CN

    更新日期：1996-06-01 00:00:00

  • Relaxation of cat trachea by beta-adrenoceptor agonists can be mediated by both beta1- and beta2-adrenoceptors and potentiated by inhibitors of extraneuronal uptake.

    abstract：:1--Responses (relaxation) to the beta-adrenoceptor agonists, isoprenaline, fenoterol or noradrenaline, were obtained on cat tracheal preparations contracted with a submaximal concentration of carbachol (0.5 microM). 2--The relative potencies of isoprenaline: fenoterol: noradrenaline were 100:8.1:10.7. From this, it wa...

    journal_title：British journal of pharmacology

    pub_type： 杂志文章

    doi：10.1111/j.1476-5381.1983.tb09406.x

    authors： O'Donnell SR,Wanstall JC

    更新日期：1983-02-01 00:00:00