Increasing evidence supports the critical role of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors in psychostimulant action. These receptors are regulated via a phosphorylation‐dependent mechanism in their trafficking, distribution, and function. The hippocampus is a brain structure important for learning and memory and is emerging as a critical site for processing psychostimulant effects. To determine whether the hippocampal pool of AMPA receptors is regulated by stimulants, we investigated and characterized the impact of amphetamine (AMPH) on phosphorylation of AMPA receptors in the adult rat hippocampus in vivo. We found that AMPH markedly increased phosphorylation of AMPA receptor GluA1 subunits at serine 845 (S845) in the hippocampus. The effect of AMPH was dose dependent. A single dose of AMPH induced a rapid and transient increase in S845 phosphorylation. Among different hippocampal subfields, AMPH primarily elevated S845 phosphorylation in the Cornu Ammonis area 1 and dentate gyrus. In contrast to S845, serine 831 phosphorylation of GluA1 and serine 880 phosphorylation of GluA2 were not altered by AMPH. In addition, surface expression of hippocampal GluA1 was up‐regulated, while the amount of intracellular GluA1 fraction was concurrently reduced in response to AMPH. GluA2 protein levels in either the surface or intracellular pool were insensitive to AMPH. These data demonstrate that the AMPA receptor in the hippocampus is sensitive to dopamine stimulation. Acute AMPH administration induces dose‐, time‐, site‐, and subunit‐dependent phosphorylation of AMPA receptors and facilitates surface trafficking of GluA1 AMPA receptors in hippocampal neurons in vivo.
The purpose of this study was to compare the effects of continuous and intermittent exercise training on serum testosterone
[T] and corticosterone concentrations [Cort] during normoxia and hypobaric hypoxia. Male rats swam with loads of 3% (normoxia)
or 2.25% (462 mmHg) body mass for 60 min in the continuous training groups, and 15 min separated by a 7-min rest × 4, with
60-min total exercise duration in the intermittent training groups, 5␣days · week−1 for 6 weeks. Serum [T] were measured at␣rest and following exercise after 6 weeks of training. Serum [Cort] were measured
immediately after an acute period of exercise or after 6 weeks of training at rest and following exercise. Continuous exercise
induced decreases in [T] under both conditions. Intermittent exercise showed a tendency to increase [T] during normoxia, but
caused a suppression during hypobaric hypoxia. The [Cort] was elevated by a similar margin after an acute period of exercise
during both conditions. After 6 weeks of training, however, [Cort] increased slightly after exercise during normoxia. A lower
resting [Cort], which was increased after exercise, was found in the training groups during hypoxia. No relevant relationship
was found between the behaviours of [T] and [Cort] after exercise during either conditions.
Accepted: 20 April 1998 相似文献
We have previously shown the presence of the glycine transporter GLYT1 in glutamatergic terminals of the rat brain. In this study we present immunohistochemical and biochemical evidence indicating that GLYT1 is expressed not only at the plasma membrane of glutamatergic neurons, but also at synaptic vesicles. Confocal microscopy, immunoblots analysis of a highly purified synaptic vesicle fraction and immunoisolation of synaptic vesicles with anti-synaptophysin antibodies strongly suggested the presence of GLYT1 in synaptic vesicles. Moreover, direct observation with the electron microscope of purified vesicles immunoreacted with anti-GLYT1 and colloidal gold demonstrated that about 40% of the small vesicles of the purified vesicle fraction contained GLYT1. Double labeling for GLYT1 and synaptophysin of this vesicular fraction revealed that more of ninety percent of them were synaptic vesicles. Moreover, a significant part of the GLYT1 containing vesicles (86%) also contained the vesicular glutamate transporter vGLUT1, suggesting a functional role of GLYT1 in a subpopulation of glutamatergic vesicles. 相似文献
Intermittent hypobaric hypoxia can produce a protective effect on both the nervous system and non-nervous system tissues. Intermittent hypobaric hypoxia preconditioning has been shown to protect rats from cardiac ischemia-reperfusion injury by decreasing cardiac iron levels and reactive oxygen species (ROS) production, thereby decreasing oxidative stress to achieve protection. However, the specific mechanism underlying the protective effect of hypobaric hypoxia is unclear. To shed light on this phenomenon, we subjected Sprague-Dawley rats to hypobaric hypoxic preconditioning (8 hours/day). The treatment was continued for 4 weeks. We then measured the iron content in the heart, liver, spleen, and kidney. The iron levels in all of the assessed tissues decreased significantly after hypobaric hypoxia treatment, corroborating previous results that hypobaric hypoxia may produce its protective effect by decreasing ROS production by limiting the levels of catalytic iron in the tissue. We next assessed the expression levels of several proteins involved in iron metabolism (transferrin receptor, L-ferritin, and ferroportin1 [FPN1]). The increased transferrin receptor and decreased L-ferritin levels after hypobaric hypoxia were indicative of a low-iron phenotype, while FPN1 levels remained unchanged. We also examined hepcidin, transmembrane serine proteases 6 (TMPRSS6), erythroferrone (ERFE), and erythropoietin (EPO) levels, all of which play a role in the regulation of systemic iron metabolism. The expression of hepcidin decreased significantly after hypobaric hypoxia treatment, whereas the expression of TMPRSS6 and ERFE and EPO increased sharply. Finally, we measured serum iron and total iron binding capacity in the serum, as well as red blood cell count, mean corpuscular volume, hematocrit, red blood cell distribution width SD, and red blood cell distribution width CV. As expected, all of these values increased after the hypobaric hypoxia treatment. Taken together, our results show that hypobaric hypoxia can stimulate erythropoiesis, which systemically draws iron away from nonhematopoietic tissue through decreased hepcidin levels. 相似文献
We have prepared highly purified synaptic vesicles from rat brain by subjecting vesicles purified by our previous method to a further fractionation step, i.e., equilibrium centrifugation on a Ficoll gradient. Monoclonal antibodies to three membrane proteins enriched in synaptic vesicles--SV2, synaptophysin, and p65--each were able to immunoprecipitate specifically approximately 90% of the total membrane protein from Ficoll-purified synaptic vesicle preparations. Anti-SV2 precipitated 96% of protein, anti-synaptophysin 92%, and anti-p65 83%. These results demonstrate two points: (1) Ficoll-purified synaptic vesicles appear to be greater than 90% pure, i.e., less than 10% of membranes in the preparation do not carry synaptic vesicle-associated proteins. These very pure synaptic vesicles may be useful for direct biochemical analyses of mammalian synaptic vesicle composition and function. (2) SV2, synaptophysin, and p65 coexist on most rat brain synaptic vesicles. This result suggests that the functions of these proteins are common to most brain synaptic vesicles. However, if SV2, synaptophysin, or p65 is involved in synaptic vesicle dynamics, e.g., in vesicle trafficking or exocytosis, separate cellular systems are very likely required to modulate the activity of such proteins in a temporally or spatially specific manner. 相似文献
目的: 探讨模拟海拔7 000 m低压低氧环境对大鼠心脏结构和功能的影响。方法: 96只雄性SD大鼠随机分为常压常氧对照组(对照组)和高原低压低氧组(低氧组)。低氧组大鼠放置于大型多因素复合环境模拟实验舱内,模拟海拔7 000 m高原环境饲养。实验舱运行时间23 h/d,控制昼夜比大约12 h∶12 h;对照组置于相同条件的常压常氧环境下饲养。低氧组又根据低氧时间不同分为3 d组、7 d组、14 d组和28 d组,同时设置与各低氧组相对应的对照组,每组均12只大鼠。应用超声心动图、心电图、血常规、血生化综合评价高原低压低氧环境下大鼠心脏结构和功能变化,心肌组织HE染色分析心肌组织病理变化。结果: 与相同时间点对照组比较①随着低压低氧暴露时间延长,大鼠体质量增长明显缓慢,动脉血氧饱和度14 d和28 d显著降低(P<0.05)。②低氧组大鼠左心室舒张末期前壁厚度(LVAWD)及左心室舒张末期后壁厚度(LVPWD)于28 d时显著升高(P<0.05)。舒张末期左心室腔直径(LVIDD)及收缩末期左心室腔直径(LVIDS)于28 d时明显降低(P<0.05,P<0.01)。左心室射血分数(EF%)、左室短轴缩短率(FS%)、肺静脉血流峰值速度(PV peak velocity)及肺静脉血流峰梯度(PV peak gradient)于低氧7 d 下降明显(P<0.05,P<0.01),低氧14 d 及低氧28 d 恢复。③低氧组大鼠心电图QRS间期与QT间期在14 d 及28 d 显著延长(P<0.05,P<0.01)。ST段3 d和7 d显著压低(P<0.05,P<0.01)。R波振幅于 7 d、14 d 及28 d 显著降低(P<0.05,P<0.01)。④低氧各组大鼠红细胞计数(RBC)、血红蛋白(HGB)、红细胞分布宽度(RDW)均明显升高(P<0.01)。血小板计数(PLT)于14 d 及28 d 明显下降(P<0.01)。血肌酐(CR)于14 d及28 d显著升高(P<0.05)。⑤心肌病理提示,低氧3 d 和7 d 可见心肌水肿、肌浆凝聚,横纹不清,灶状变性和坏死伴炎性细胞浸润。低氧14 d 和28 d 心肌组织炎症性病理损伤逐渐减少。心肌细胞逐渐肥大,成纤维细胞逐渐增生。心肌间质胶原纤维逐渐增多等心肌代偿修复性病理变化显著。结论: 暴露于模拟海拔7 000 m低压低氧环境下3 d大鼠心功能明显降低,7 d最为显著。 相似文献