Effect of Prenatal Hypobaric Hypoxia on Glutamatergic Signal Transduction in Rat Brain

Ca²⁺-mediated signal transduction of group I metabotropic glutamate receptors (ImGluR) was studied in the brain of young (15 days) and old rats (90 days) exposed to severe hypobaric hypoxia on gestation days 14–16. Changes in the concentration of bound intracellular Ca²⁺ (Ca²⁺ response) were evaluated after repeated application of a selective ImGluR agonist 3,5-dihydroxyphenylglycine (DHPG) to cultured brain slices. Primary application of DHPG for 2 min induced a negative Ca²⁺ response in slices from 15-day-old intact animals, while repeated application caused a positive response. In slices from 90-day-old control animals, both responses were negative. In slices from rats of both age groups subjected to severe prenatal hypobaric hypoxia, both responses were mainly positive, but short-term negative components were present in adult animals. Our results suggest that severe hypobaric hypoxia changes the balance between the two constitutive signal pathways triggered by ImGluR (inosine triphosphate and diacylglycerol pathways). This procedure is followed by the increased influx of extracellular Ca²⁺ (as compared to Ca²⁺ release from the intracellular stores). This imbalance is particularly pronounced at the early stage of ontogeny.     

Moderate Hypobaric Hypoxia Modifies Ca<Superscript>2+</Superscript>-Mediated Glutamatergic Signal Transduction in Rat Cerebral Cortex

Examination of fluorescent Ca²⁺-responses to stimulation by ionotropic glutamate receptor agonists in rat cerebral cortex slices, preconditioned with hypobaric hypoxia, has demonstrated different time course for up-regulation of their Ca²⁺-conductivity and for stimulation of the consequent binding of the Ca²⁺ which entered the cell. The evident result is the development of AMPA-mediated moderate increase of intracellular Ca²⁺. Translated from Byulleten’ Experimental’noi Biologii i Meditsiny, Vol. 147, No 2, pp. 144–147, February, 2009     

Morphological Changes and Characteristics of the Expression of Serine Racemase in the Rat Hippocampus after Repeated Exposure to Negative Gravitational Overload

Neuroscience and Behavioral Physiology - Objectives: To study the morphometric parameters and levels of expression of serine racemase in the rat hippocampus after repeated gravitational overloading...     

应激对模拟高原低压低氧环境下大鼠海马单胺递质的影响

目的:探讨心理和生理应激对模拟高原低压低氧环境下大鼠海马单胺递质含量的影响。方法:用旁观电击的方法建立大鼠心理和生理应激模型。低氧处置为将大鼠置于模拟海拔6000m的低压舱内24小时。比较不同方式和强度的应激对低压低氧性环境下大鼠海马细胞外液中去甲肾上腺素(NE),多巴胺(DA),高香草酸(HVA)和5-羟色胺(5-HT)含量的影响。用高效液相色谱-电化学法检测其中的单胺递质的含量。结果:(1)低氧组大鼠海马细胞外液中NE含量低于正常对照组(813.8±196.1/1209.2±282.0,P<0.01);心理性(应激2次 低氧组:906.0±227.6,应激4次 低氧组:1103.7±270.6)和生理性(应激2次 低氧组990.3±93.7,应激4次 低氧组:610.8±104.1)应激 低氧组大鼠海马NE含量均高于低氧环境下(813.8±196.1)大鼠(P<0.05)。(2)低氧组大鼠海马细胞外液中5-HT含量高于正常对照组(82.7±23.4/52.3±27.9,P<0.05);生理应激2次 低氧组5-HT含量高于低氧组(134.2±51.5/82.7±23.3),生理应激4次 低氧组5-HT含量则低于低氧组(41.9±13.4/82.7±23.4,P<0.05)。结论:不同方式和强度的应激对低压低氧环境下大鼠海马单胺递质的影响存在差异。     

不同应激方式对模拟高原环境下大鼠海马单胺递质的影响

目的:探讨心理和生理应激对模拟高原低压低氧环境下的大鼠海马单胺递质含量的影响。方法:雄性SD大鼠随机分为对照组(Con组)、低氧组(Hy组)、心理应激(2次/d)组(Ps1组)、心理应激(2次/d×2天)组(Ps2组)、心理应激(2次/d) 低氧组(Ps1 Hy组)、心理应激(2次/d×2天) 低氧组(Ps2 Hy组)、生理应激(2次/d)组(Ph1组)、生理应激(2次/d×2天)组(Ph2组)、生理应激(2次/d) 低氧组(Ph1 Hy组)和生理应激(2次/d×2天) 低氧组(Ph2 Hy组)。心理和生理应激都采用旁观电击(CB)的方法。用高效液相色谱-电化学检测法(HPLC-ECD)测定用推挽灌流收集的海马灌流液中的去甲肾上腺素(NE),多巴胺(DA)和5-羟色胺(5-HT)的含量。结果:①与Con组比较,Hy、Ps1 Hy和Ph2 Hy组的NE含量均显著降低(P<0.01,0.05和0.01);与Hy组比较,Ps2 Hy和Ph1 Hy组的NE含量均显著增高(P<0.01和0.05)。②与Con和Hy组比较,Ph1 Hy组的5-HT含量均显著升高(P<0.01和0.05)。③与Con和Hy组比较,Ph1 Hy组的DA含量均显著升高(P<0.01)。结论:心理和生理应激皆能显著影响低压低氧环境下大鼠海马单胺递质的含量。     

不同的应激方式对模拟高原环境下肺损伤影响的实验研究

目的探讨心理和生理应激对模拟高原低压低氧环境下大鼠肺损伤的影响。方法雄性SD随机分为对照组（Con组）、低氧组（Hy组）、心理应激（2次／天）组（Ps1组）、心理应激（2次／天×2天）组（Ps2组）、心理应激（2次／天）＋低氧组（Ps1＋Hy组）、心理应激（2次／天×2天）＋低氧组（Ps2＋Hy组）、生理应激（2次／天）组（Ph1组）、生理应激（2次／天×2天）组（Ph2组）、生理应激（2次／天）＋低氧组（Ph1＋Hy组）和生理应激（2次／天×2天）＋低氧组（Ph2＋Hy组）。心理和生理应激都采用旁观电击（CB）的方法。通过测定大鼠右肺湿／干比值、全湿肺／体重比值、右肺含水比值、与细支气管伴行小血管“袖套”面积和血管的“袖套”面积／血管面积的比值来评定肺损伤的程度。结果①与Con和Hy组比较,Ps2＋Hy、Ph1＋Hy和Ph2＋Hy组的右肺湿／干比值均显著增高（P分别〈0．05和0．01）;②与Con和Hy组比较,Ph1＋Hy和Ph2＋Hy组的肺含水比值均显著增高（P均〈0．01）;③与Con和Hy组比较,Ps2＋Hy、Ph1＋Hy和Ph2＋Hy组血管“袖套”面积和血管“袖套”面积／血管面积比值均显著增高（P分别〈0．05和0．01）。结论心理和生理应激均可加重急性低压低氧环境导致的大鼠肺损伤。     

Systemic Hypoxia and the Depression of Synaptic Transmission in Rat Hippocampus after Carotid Artery Occlusion

The relationship between step reductions in inspired oxygen and the amplitude of evoked field excitatory postsynaptic potentials (fEPSPs) recorded from hippocampal CA1 neurons was examined in anaesthetized rats with a unilateral common carotid artery occlusion. The amplitudes of fEPSPs recorded from the hippocampus ipsilateral to the occlusion were significantly more depressed with hypoxia than were the fEPSPs recorded from the contralateral hippocampus. The adenosine A₁-selective antagonist, 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), blunted the hypoxic depression of the fEPSP. Tissue partial pressure of oxygen ( P _tiss,O2) was measured in the ipsilateral and contralateral hippocampus using glass Clark-style microelectrodes. P _tiss,O2 fell to similar levels as a function of inspired oxygen in the ipsilateral and contralateral hippocampus, and in the ipsilateral hippocampus after administration of 8-CPT. Hippocampal blood flow (HBF) was measured using laser Doppler flowmetry. A decline in HBF was associated with systemic hypoxia in both hippocampi. HBF, as a function of inspired oxygen, fell significantly more in the ipsilateral than in the contralateral hippocampus. We conclude that endogenous adenosine acting at the neuronal A₁ receptor plays a major role in the depression of synaptic transmission during hypoxic ischaemia. The greater susceptibility of the fEPSP in the ipsilateral hippocampus to systemic hypoxia cannot be explained entirely by differences in P _tiss,O2 or HBF between the two hemispheres.     

心理应激对模拟高原低压低氧环境下大鼠海马单胺递质的影响

目的探讨心理应激对模拟高原低压低氧环境下大鼠海马单胺递质含量的影响。方法用旁观电击的方法建立大鼠心理应激模型。低氧处置为将大鼠置于模拟海拔6000m的低压舱内24小时。观察下列心理应激对低压低氧环境下大鼠海马细胞外液中去甲肾上腺素（NE），多巴胺（DA）和5-羟色胺（5-HT）含量的影响。用高效液相色谱-电化学法检测其中的单胺递质的含量。结果①低氧能显著降低大鼠海马细胞外液中NE的含量（P〈0.01）；心理性能显著增加低氧环境下NE的含量（P〈0.01）；②低氧能显著增加大鼠海马细胞外液中5-HT的含量（P〈0.01）；心理应激不能进一步增加低氧环境下5-HT的含量。结论心理应激能影响低压低氧环境下大鼠海马单胺递质的含量。     

Histochemical and Morphological Changes in Various Regions of the Rat Hippocampus in Swimming-Induced Stress

Swimming stress increased the functional activity of hippocampal pyramidal neurons in rats, as indicated by decreases in their glycogen contents and increases in their nucleic acid contents and the nucleus:cytoplasm ratio. These changes were most marked in hippocampal field CA1, while changes in other regions of the hippocampus were minimal.     

Changes in Histone H3 Acetylation in the Rat Hippocampus Due to Severe Hypoxia and the Role of Hypoxic Postconditioning

Neuroscience and Behavioral Physiology - Objective. To study the effects of severe hypobaric hypoxia followed by sessions of moderate hypobaric hypoxia using a postconditioning regime (PostC) with...     

人铜锌超氧化物歧化酶的基因工程研究 Ⅱ.人铜锌超氧化物歧化酶在大肠杆菌中的表达

利用pUC 8为载体质粒,将合成的人Cu/Zn SOD基因置于Lac Z启动子的调控下,构建了含有该基因的表达质粒pCZS Ⅰ。首次成功地在大肠杆菌中表达了合成人Cu/Zn SOD的基因。SDS聚丙烯酰胺凝胶电泳薄层扫描分析证明,SOD基因的表达产物占细胞可溶性蛋白质的13％左右,用光扩增法捡测表达产物的酶活性,每毫克蛋白质为48.6 McCord Fridovich单位。     

Spatiotemporal Expression of HDAC2 during the Postnatal Development of the Rat Hippocampus

Background: Histone acetylation, which is a chromatin modification of histone tails, can dynamically regulate the expression of various genes in normal development. HDAC2 is a negative regulatory factor of acetylation and closely related to learning and memory. NSE is a nerve marker and vital for maintaining physiological functions in nervous system. Currently, few studies associated with the expression pattern of HDAC2 in postnatal rat hippocampus have been reported. This study aimed to explore the temporal and spatial expression pattern of HDAC2, helping to reveal the expression characteristics of HDAC2 during postnatal neuronal maturation. Materials and Methods: With NSE as a biomarker of neuronal maturation at postnatal days 1, 3, 7 and weeks 2, 4, and 8 (P1D, P3D, P7D, P2W, P4W, P8W), the expression patterns of HDAC2 in rat hippocampus were examined using real-time PCR and western blotting. Additionally, the subcellular distribution of HDAC2 was analysed by immunofluorescence. Results: We found that HDAC2 was highly expressed in the neonatal period and decreased gradually. HDAC2 expression was widely distributed in neurons of hippocampal CA1, CA3 and DG regions and gradually shifted from the nucleus to the cytoplasm during postnatal development. Altogether, the expression of HDAC2 decreased gradually with different subcellular localizations throughout development. Conclusions: The observed results indicate that the expression levels of HDAC2 become lower and with different subcellular localizations in neurons during hippocampal neuronal maturation, suggesting the specific expression characteristics of HDAC2 might play an important role during postnatal learning-memory function and development.     

Structural Changes in the Elements of the Blood-Brain Barrier of the Hippocampus in Rats after Exposure to Perinatal Hypoxia and the Potential for Their Pharmacological Correction

Neuroscience and Behavioral Physiology - Objectives. To study the dynamics of structural changes in elements of the blood-brain barrier of the hippocampus during the early postnatal period and...     

Endothelial Gene Expression in Regions of Defined Shear Exposure in the Porcine Iliac Arteries

The effect of hemodynamic shear stress on endothelial gene expression was investigated in the porcine iliac arteries. A novel statistical approach was applied to computational fluid dynamics simulations of the iliac artery flow field to identify three anatomical regions likely to experience high, medium, and low levels of time average shear stress magnitude. Subsequently, endothelial cell mRNA was collected from these regions in the iliac arteries of six swine and analyzed by DNA microarray. Gene set enrichment analysis demonstrated a strong tendency for genes upregulated or downregulated in one of the extreme shear environments (low or high, relative to medium) to be regulated in the same direction in the other extreme shear environment. This tendency was confirmed for specific genes by real-time quantitative PCR. Specifically, β-catenin, c-jun, VCAM-1, and MCP-1 were all upregulated in low and high shear stress regions relative to the medium shear stress region. eNOS expression was not significantly different in any of the regions. These results are consistent with the notion that endothelial cells chronically exposed to abnormally low or high shear levels in vivo exhibit similar genetic responses. Alternative explanations of this outcome are proposed, and its implications for the role of shear stress in atherogenesis are examined.