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排序方式: 共有765条查询结果,搜索用时 31 毫秒
71.
72.
Louisa Lyon Philip WJ Burnet James NC Kew Corrado Corti J Nicholas P Rawlins Tracy Lane Bianca De Filippis Paul J Harrison David M Bannerman 《Neuropsychopharmacology》2011,36(13):2616-2628
Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3−/−) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals'' exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3−/− mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive and exploratory spatial memory tasks may be absent in aversive tasks because the latter induce higher levels of arousal, which rescue spatial learning. Consistent with an altered arousal–cognition relationship in GRM2/3−/− mice, injection stress worsened appetitively motivated, spatial working memory in wild-types, but enhanced performance in GRM2/3−/− mice. GRM2/3−/− mice were also hypoactive in response to amphetamine. This fractionation of hippocampus-dependent memory depending on the appetitive-aversive context is to our knowledge unique, and suggests a role for group II mGluRs at the interface of arousal and cognition. These arousal-dependent effects may explain apparently conflicting data from previous studies, and have translational relevance for the involvement of these receptors in schizophrenia and other disorders. 相似文献
73.
INTRODUCTION/PURPOSE: Negative mood symptoms occur frequently in sedentary populations, but individual vulnerability factors for developing these complaints have not been systematically evaluated. This investigation examined whether the autonomic nervous system (ANS) serves a role in the development of negative mood after controlled exercise withdrawal. METHODS: Forty participants (mean age of 31.3 +/- 7.5 yr, 55% women) who exercised regularly (>or= 30 min of continuous aerobic exercise at least three times a week during the past 6 months) were randomized either to withdrawal from regular aerobic exercise (N=20) or to continue regular aerobic exercise (N=20) for 2 wk. Measurements were taken before exercise withdrawal and at 2-wk follow-up. Various dimensions of negative mood were measured with the multidimensional fatigue inventory, profile of mood states, and Beck depression inventory-II. ANS activity was assessed by heart rate variability (HRV) analyses, examining low-frequency (0.04-0.15 Hz: lf) and high-frequency (hf) domains (0.15-0.40 Hz). The lf/hf ratio was used as index of sympathovagal balance. Protocol adherence was documented by ambulatory activity monitoring. RESULTS: Exercise withdrawal resulted in significantly higher negative mood scores at follow-up compared with control (P<0.05). Baseline lf/hf ratios correlated with the increases in symptoms (r>0.4; P<0.05) in the exercise-withdrawal group independently of gender, age, weight, baseline fitness level, and baseline symptom status. The exercise-withdrawal and control groups displayed no significant change in hf HRV, lf HRV, or lf/hf HRV during the 2 wk. CONCLUSION: Reduced parasympathetic ANS activity as measured by HRV is predictive of the development of negative mood after deprivation of usual exercise activities. No significant changes in HRV were observed during the 2-wk exercise deprivation period. These findings are relevant to the understanding of mood changes in response to short-term exercise withdrawal, such as sports injuries and recovery from medical procedures. 相似文献
74.
75.
Robert M. Hoek Daphne de Launay Else N. Kop A. Seda Yilmaz‐Elis Feng Lin Kris A. Reedquist J. Sjef Verbeek M. Edward Medof Paul P. Tak Jrg Hamann 《Arthritis \u0026amp; Rheumatology》2010,62(4):1036-1042
Objective
CD55 (decay‐accelerating factor) is best known for its role in the negative regulation of the complement system. Indeed, lack of this molecule leads to disease aggravation in many autoimmune disease models. However, CD55 is abundantly present on fibroblast‐like synoviocytes and is also a ligand of the adhesion‐class heptahelical receptor CD97, which is expressed by infiltrating macrophages. Treatment with antibodies to CD97 ameliorates the collagen‐induced model of rheumatoid arthritis (RA) in DBA/1 mice, but the net contribution of CD55 is unknown. This study was undertaken to investigate the role of CD55 in experimental RA.Methods
Arthritis was induced in wild‐type, CD55−/−, and CD97−/− mice using collagen‐induced and K/BxN serum–transfer models. Incidence of arthritis was monitored over time, and disease activity was assessed by clinical and immunohistochemical evaluation.Results
In contrast to observations in many inflammatory disease models, lack of CD55 resulted in decreased arthritis in experimental models of RA. Consistent with the previously reported effects of anti‐CD97 antibody treatment, CD97−/− mice had reduced arthritis activity compared with wild‐type controls.Conclusion
Our findings indicate that the lack of CD55 or CD97 in 2 different models of arthritis increases resistance to the disease. These findings provide insight into a role for CD55 interaction with CD97 in the pathogenesis of RA and suggest that therapeutic strategies that disrupt CD55/CD97 may be clinically beneficial.76.
77.
78.
P van Ruitenbeek A Sambeth A Vermeeren SN Young WJ Riedel 《British journal of pharmacology》2009,157(1):92-103
Background and purpose:
Animal studies show that histamine plays a role in cognitive functioning and that histamine H3-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H1-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.Experimental approach:
Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.Key results:
Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.Conclusions and implications:
L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H1-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies. 相似文献79.
Z Luo Y Chen S Chen WJ Welch BT Andresen PA Jose CS Wilcox 《British journal of pharmacology》2009,157(6):935-943
Background and purpose:
We compared the dose-dependent reductions in cellular superoxide anion (O2−) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3′,4′,5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, α-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox).Experimental approach:
O2− was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence.Key results:
SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O2− of 80–90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50–70%), whereas trolox, α-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O2− was increased by NAC and NBT at low concentrations but reduced at high concentrations.Conclusions and implications:
Maximum effectiveness against cellular production of O2− requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O2− production. Vitamins C and E or analogues have low efficacy. 相似文献80.