Abstract:
:Synaptic pathology is associated with protein accumulation events, and is thought by many to be the best correlate of cognitive impairment in normal aging and different types of dementia including Alzheimer's disease. Numerous studies point to the disruption of microtubule-based transport mechanisms as a contributor to synaptic degeneration. Reported reductions in a microtubule stability marker, acetylated alpha-tubulin, suggest that disrupted transport occurs in Alzheimer's disease neurons, and such a reduction is known to be associated with transport failure and synaptic compromise in a hippocampal slice model of protein accumulation. The slice model exhibits accumulated proteins in response to chloroquine-mediated lysosomal dysfunction, resulting in corresponding decreases in acetylated tubulin and pre- and postsynaptic markers (synaptophysin and glutamate receptors). To test whether the protein deposition-induced loss of synaptic proteins is due to disruption of microtubule integrity, a potent microtubule-stabilizing agent, the taxol derivative TX67 (10-succinyl paclitaxel), was applied to the hippocampal slice cultures. In the absence of lysosomal stress, TX67 (100-300 nM) provided microtubule stabilization as indicated by markedly increased levels of acetylated tubulin. When TX67 was applied to the slices during the chloroquine treatment period, pre- and postsynaptic markers were maintained at control levels. In addition, a correlation was evident across slice samples between levels of acetylated tubulin and glutamate receptor subunit GluR1. These data indicate that disruption of microtubule integrity accounts for protein deposition-induced synaptic decline. They also suggest that microtubule-stabilizing drugs can be used to slow or halt the progressive synaptic deterioration linked to Alzheimer-type pathogenesis.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Butler D,Bendiske J,Michaelis ML,Karanian DA,Bahr BAdoi
10.1016/j.ejphar.2007.01.053subject
Has Abstractpub_date
2007-05-07 00:00:00pages
20-7issue
1-2eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00116-1journal_volume
562pub_type
杂志文章abstract::The objective of the present studies was to investigate the effect of voluntary ethanol consumption for 21 days on the brain beta-endorphin system of C57BL/6 (alcohol-preferring) and DBA/2 (alcohol-avoiding) strains of mice. As expected, C57BL/6 mice consumed a significantly higher quantity of the 10% ethanol solution...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90064-7
更新日期:1994-06-02 00:00:00
abstract::The prevention of the decrease in neostriatal tryptophan hydroxylase (TPH) activity with a single dose of methamphetamine (MA) was attempted by lesioning the nigrostriatal dopaminergic projections with bilateral nigral injections of 6-hydroxydopamine (6-OHDA). The rats were injected with MA (10 mg/kg) 11 days later, a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90616-9
更新日期:1987-03-17 00:00:00
abstract::In mature spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, acetylcholine, the calcium ionophore A 23187 and ATP release endothelium-derived contracting factor (EDCF), cyclooxygenase (COX) derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by ace...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.10.050
更新日期:2007-02-05 00:00:00
abstract::The convulsant, anticonvulsant and anaesthetic activities of a series of 6 barbiturates related to pentobarbitone have been qualitatively and quantitatively determined in mice. The presence or absence of convulsant activity was strongly dependent on molecular structure and there were marked variations in potency among...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90575-1
更新日期:1982-04-08 00:00:00
abstract::The potent alpha-adrenergic agonist DPI, which has also been claimed to be a selective dopaminergic agonist, was shown to reduce rat striatal dopamine (DA) synthesis, DA utilization and DA metabolism following intraperitoneal administration (25 mumol/kg). An analytical procedure for the determination of DPI was develo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90603-3
更新日期:1982-06-16 00:00:00
abstract::Iron overload cardiomyopathy is the major cause of death in transfusion-dependent thalassemia (TDT) patients. Growing evidence demonstrates that combined iron chelators, or the combination of an iron chelator with antioxidant(s) are effective in diminishing myocardial iron deposition and attenuating cardiac dysfunctio...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2015.08.017
更新日期:2015-10-15 00:00:00
abstract::Sex and stress hormones coordinate experience and behaviour with physiological regulations. In the brain the sex hormones act to promote the repertoire of affiliative and reproductive behaviours. Stress hormones target in particular brain circuits underlying emotional arousal and cognition. To exert these actions the ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2009.10.017
更新日期:2010-01-10 00:00:00
abstract::Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Once trained, the rats were tested with the ED50 of apomorphine (0.02 mg/kg) or saline before and 1-22 days after a ten-day regimen of daily 2.0 mg/kg admi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90053-4
更新日期:1981-09-24 00:00:00
abstract::The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90502-w
更新日期:1990-06-21 00:00:00
abstract::The influence of native low-density lipoprotein (LDL) on the inhibition of endothelium-dependent relaxation previously induced by oxidized LDL was investigated with intact rabbit aortic rings. We also tried to assess oxysterol involvement in the native lipoprotein effects. Lipoprotein fractions (1 mg protein/ml) were ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00696-8
更新日期:2000-10-20 00:00:00
abstract::The significance of the blood pressure elevation caused by N(G)-nitro-L-arginine (L-NNA) to inhibitory mechanism of the drug on depressor responses to acetylcholine in anesthetized dogs was investigated. L-NNA (50 mg kg(-1), i.v.) elevated blood pressure to a plateau of 30-50 mm Hg above baseline level and shifted the...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00288-5
更新日期:1999-06-04 00:00:00
abstract::Carbachol produces both negative and positive inotropy in rat left atria. It is not clear whether these two effects are mediated by two separate cell surface muscarinic receptors or a single receptor interacting with two coupling proteins in the cell membrane. Pirenzepine, known to selectively block some biochemical m...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94095-f
更新日期:1990-11-20 00:00:00
abstract::Nitric oxide (NO) is present in the exhaled breath of humans and other mammalian species. It is generated in the lower airways by enzymes of the nitric oxide synthase (NOS) family, although nonenzymatic synthesis and consumptive processes may also influence levels of NO in exhaled breath. The biological properties of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2005.12.069
更新日期:2006-03-08 00:00:00
abstract::We previously reported that the functional deletion of p21, a cyclin-dependent kinase inhibitor, in mice attenuated renal cell senescence in streptozotocin (STZ)-induced type 1 diabetic mice. In the present study, we investigated the effect of iron chelation on renal cell senescence and inflammation in the type 1 diab...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2015.03.053
更新日期:2015-06-05 00:00:00
abstract::The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) on central monoamine neurons in mice was investigated using histo- and biochemical techniques. NMPTP (2 X 10 mg/kg i.v.) produced a rapid and long-lasting reduction (-30%) of striatal dopamine, while the dopamine levels were only transiently reduced in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90521-1
更新日期:1984-01-13 00:00:00
abstract::In rats adapted to a +30 degrees C temperature for one week, transfer to a temperature of +4 degrees C increased immunoassay-able serum TSH from 150-300 ng/ml to 800-2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenza...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90103-x
更新日期:1975-02-01 00:00:00
abstract::Nicotine is one of the most representative components in cigarette smoke leading to gastric ulceration. Both ornithine decarboxylase and potassium ion (K(+)) channels are essential for cell growth and wound repair. The aim of the present study is to elucidate the causative relationship of these two factors during woun...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01610-2
更新日期:2002-05-24 00:00:00
abstract::Lesions of the nucleus basalis magnocellularis and the medial septal area have been shown to produce both deficits in memory and decreases in choline acetyltransferase levels. In order to determine whether functional changes in acetylcholine receptor sensitivity also occur, the present experiment examined the ability ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90619-x
更新日期:1988-08-24 00:00:00
abstract::The effects of various subcutaneous doses (30, 100 and 300 micrograms/kg) of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a serotonin (5-HT)1A receptor agonist, were studied on the performance of rats in a one-trial passive avoidance task. When administered 30 min before the training trial and the retention tes...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90533-a
更新日期:1992-02-11 00:00:00
abstract::Ketamine, a non-selective inhibitor of NMDA (N-methyl-D-aspartate) channels is used in anesthetic or sub-anesthetic doses to induce analgesia, amnesia, to suppress fear, anxiety and depression. Although the ketamine's effect on memory acquisition is known, its effects on other aspects of memory are controversial. Morr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.12.021
更新日期:2012-02-29 00:00:00
abstract::Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide with potent trophic and protective effects on brain neurons, glia and endothelia. In previous studies, we showed that intravenously administered bFGF reduced the volume of cerebral infarcts following permanent occlusion of the middle cerebral arter...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)89672-0
更新日期:1997-05-26 00:00:00
abstract::Unexpectedly, it was observed that the P2-purinoceptor antagonist, suramin (10 microM to 1 mM), reversed the muscle paralysis caused by structurally unrelated non-depolarizing relaxants. Suramin competitively reversed the blocking action of pancuronium. Both the pre- and postsynaptic blockade of nicotinic receptors by...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90211-l
更新日期:1992-05-27 00:00:00
abstract::Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, has been reported to have anti-inflammatory and protective effects in ischemia heart etc. However, whether it can mitigate behavioral alterations induced by sleep deprivation, has not yet been elucidated. Numerous studies have demonstrated that...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.02.036
更新日期:2011-05-11 00:00:00
abstract::Type 2 diabetes is increasing at epidemic proportions throughout the world, and diabetic nephropathy is the principal cause of end stage renal failure. Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury. The a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.11.029
更新日期:2011-02-25 00:00:00
abstract::We previously reported the synthesis of three new opioid agonists as well as their in vitro and in vivo activity [Girón, R., Abalo, R., Goicoechea, C., Martín, M.I., Callado, L.F., Cano, C., Goya, P., Jagerovic, N. 2002. Synthesis and opioid activity of new fentanyl analogs. Life Sci. 71, 1023-1034]. One of them, N-[1...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.07.052
更新日期:2008-10-24 00:00:00
abstract::Detailed antagonist competition curves for [3H]prazosin-labelled binding sites in rat cerebral cortex membranes reveal anomalous binding characteristics. Dihydroergocryptine and indoramine compete in a steep, monophasic manner while WB4101 and phentolamine exhibit shallow competition curves. Computer-assisted analysis...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90432-7
更新日期:1985-02-26 00:00:00
abstract::Adenosine (10(-4)-10(-3) M) contracted the isolated rat tail artery. This effect exhibited rapidly developing tachyphylaxis. Methysergide (10(-7) M) prevented the contractile response to adenosine and 5-hydroxytryptamine (5-HT) without affecting that to noradrenaline. Pretreatment of rats with parachlorophenylalanine ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90513-6
更新日期:1981-12-03 00:00:00
abstract::As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat bladder dome. The density of endothelin receptors in the rat bladder dome was higher (8 and 16 weeks f...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00753-0
更新日期:2000-01-17 00:00:00
abstract::The extracellular loops of the adrenoceptors present a potential therapeutic target in the design of highly selective adrenergic drugs. These regions are less conserved than the orthosteric binding site but have to date not been implicated in activation of adrenoceptors. A previously generated homology model identifie...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.03.034
更新日期:2014-06-15 00:00:00
abstract::To investigate the role of ATP-sensitive K+(KATP) channels on pacemaker activity in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and intracellular Ca2+([Ca2+]i) imaging were performed in cultured colonic ICC. Pinacidil (a K+ channel opener) hyperpolarized the membrane and inhibited the generat...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.05.029
更新日期:2017-08-15 00:00:00