Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats

The exogenously hypercholesterolemic (ExHC) rat is an established strain that exhibits a polygenic syndrome of hypercholesterolemia after feeding on a cholesterol-containing diet, and the extent of this differs between male and female rats in the strain. The present study was performed to determine the genetic background of diet-induced hypercholesterolemia in ExHC rats. We used quantitative trait locus (QTL) analyses of the F2 progeny derived from ExHC and Brown-Norway rats. Rats were fed a diet containing 1% cholesterol, and a genome-wide scan was then performed. Significant QTLs for serum total cholesterol levels were revealed on chromosomes 5 and 14 in the vicinity of markers D5Rat95 and D14Rat43, having maximum logarithm of the odds scores of 6.0 and 5.8, respectively. A suggestive QTL for the trait was also detected on chromosome 3 at D3Rat140. In particular, the QTL on chromosome 5 was specific for female rats. These loci were novel QTLs for post-dietary serum total cholesterol levels. In addition, cross-mating analysis in F1 generations suggested that the responsiveness to dietary cholesterol in ExHC rats is partly attributable to X-linked inheritance. Identifying such genetic factors may be useful in predicting the risks associated with diet-induced hypercholesterolemia in humans.     

急性低压低氧对大鼠空间学习记忆的影响及与海马内孤啡肽的关系

目的:研究暴露在不同海拔高度的急性低压低氧环境中,大鼠空间学习记忆能力的变化及与海马内孤啡肽的关系.方法:采用低压舱模拟4 500 m(中度)和7 500 m(重度)两种海拨高度,Morris水迷宫训练方法和反转录多聚酶链式反应(RT-PCR)技术.结果:①海马内孤啡肽mRNA表达在急性重度低压低氧(8 h/d,连续6 d)后明显增加,然而在Morris 水迷宫训练(6 counts/d,连续6 d,定位航行潜伏期逐渐缩短)后则显著降低.②急性低压低氧后,定位航行潜伏期明显延长,而海马内孤啡肽mRNA表达较学习记忆训练组明显升高.结论:海马内孤啡肽参与急性低压低氧降低大鼠空间学习记忆的机制.     

慢性复合应激增强大鼠空间学习和记忆能力

本文观察了慢性复合应激对大鼠学习与记忆功能的影响。实验采用成年 Wistar 大鼠, 将其随机分成应激组和对照组。采用垂直旋转、睡眠剥夺、噪音刺激和夜间光照4 种应激原, 无规律地交替刺激动物 6 周, 每天6 h, 制作慢性复合应激动物模型。采用 Morris 水迷宫和 Y- 迷宫测试大鼠学习与记忆成绩,并用 Cresyl violet 染色法对大鼠海马结构进行神经细胞计数。结果显示,应激组动物慢性复合应激后, 在 Morris 水迷宫内寻找隐蔽平台所需的时间(潜伏期)比对照组的明显地短(P<0.05), 表明应激鼠的空间记忆能力明显强于对照鼠;在 Y- 迷宫内寻找安全区的正确率比对照组的明显地高(P<0.05), 表明应激鼠的明暗分辨学习能力明显强于对照鼠; 应激鼠慢性复合应激后, 其海马结构齿状回、CA3 和CA1 区神经细胞密度极明显地高于对照鼠(P<0.001)。这些结果提示, 慢性复合应激可增强大鼠空间记忆能力和明暗分辨学习能力。本文并对慢性复合应激模式增强大鼠学习和记忆能力的可能原因进行了讨论。     

学习训练对谷氨酸单钠所致大鼠海马损伤的神经保护作用

目的：探讨学习训练对谷氨酸神经毒性的保护作用。方法：在SD大鼠生后第3～9d腹腔注射谷氨酸单钠复制谷氨酸毒性模型,在1月龄和2月龄时训练大鼠学会以明暗辨别来获得食物,3月龄时取脑,在光镜下计数海马内存活神经元数,电镜下观察海马CA1区的超微结构,并计数突触数,测量突触活性带长度。结果：学习训练组海马CA3区和CA4区内的存活神经元数、海马CA1区内的突触数和突触活性带长度均大于非学习组,结论：结果提示学习训练可在一定程度上减轻MSG对海马的损伤。     

Single particle analysis of manganese-induced prion protein aggregates

Prion diseases are characterized by the conversion of the cellular prion protein (PrP(C)) to a disease-specific aggregated isoform (PrP(Sc)). We have shown that Mn(2+) ions amplify aggregation, whereas Cu(2+) has an inhibitory effect. To characterize Mn(2+)-induced aggregates, we used cross-correlation analysis as well as scanning for intensely fluorescent targets in an SDS-dependent aggregation assay with fluorescently labeled PrP. We found that the effect of Mn(2+) was mainly due to the association of preformed PrP oligomers to larger aggregates, rapidly reversible by EDTA, and independent of the histidine-dependent copper-binding sites of PrP, suggesting that Mn(2+) induces reversible intermolecular binding. In contrast, the inhibitory effect of Cu(2+) required binding to histidine-containing binding sites, indicating that binding of copper affects the structure of PrP(C) which in turn modifies the susceptibility to manganese and the ability to aggregate. These findings suggest that copper and manganese may also affect prion propagation in vivo.     

Effects of special brain area regional cerebral blood flow abnormal perfusion on learning and memory function and its molecular mechanism in rats

To study the effect of special brain area regional cerebral blood flow (rCBF) abnormal perfusion on learning and memory function and its molecular mechanism, 64 adult male healthy Sprague-Dawley (SD) rats were randomly divided into two groups, the false operation group (control group) and the operation group (model group). After surgical operation, the operation group undertook bilateral common carotid artery permanent ligation, while the other group did not. Learning and memory function were measured by Y-maze at 4 h, 8 h, 24 h and 3 d after surgical operation, respectively. The rCBF of the right frontal lobe and hippocampus was also detected by the PerifluxPF model laser Doppler flowmetry, and the expressions of c-fos or c-jun or Bcl-2 and Bax were also measured by immune histochemistry S-P method accordingly. Results showed that the rCBF of the right frontal lobe and hippocampus in the operation group was significantly lower than that in the false operation group (P < 0.05). The learning indexes, error number (EN), day of reach standard and total reaction time (TRT) in the operation group, were significantly higher than that in the false operation group (P < 0.05). However, the initiative evasion rate in the operation group was significantly lower than that in the false operation group. The study also found that the rCBF was relatively more, the indexes (EN, the day of reach standard and TRT) relatively fewer, but the initiative evasion rate and the memory keeping rate were relatively more. The positive expression and the average absorbency of Fos and Jun in the operation group were significantly higher than that in the false operation group (P < 0.05). Furthermore, Bax and Bcl-2 positive cells were all increased over time in the operation group, and the expression ratio of Bax/Bcl-2 in the operation group was significantly higher than that in the false operation group (P < 0.01). In conclusion, rCBF decrease can impair the learning and memory function in rats, which may be related to the increase of the expression ratio of c-fos or c-jun or Bcl-2 or Bax in the frontal cortex and hippocampus.     

The effect of altered selenium and vitamin E nutritional status on learning and memory of third-generation rats

It has been proposed that selenium (Se) and Vitamin E (Vit E) are involved synergistically in protection of cell membrane lipids from peroxidation. However, little is known about the effect of both deficiencies of Se and Vit E and toxic status of those antioxidants on the peroxidation potentiality of the brain. We aimed to study the effects of both Se and Vit E inadequate diet and Se rich diet on the learning and memory processes of third-generation young rats. Their ancestors were also fed by the same diets starting from their births. To test the learning and memory, the rats aged 60 days were trained by using automated two ways active avoidance shuttle box. The acquisition tests were terminated with training the rat from each group to be 25 trials per day during three days. Ten days after the last acquisition test, the retention test was performed and the acquisition of the conditioned avoidance responses (CAR) of the rats were evaluated. It is demonstrated that the CAR of all rats from three groups showed a significant increase in three consecutive days while the differences observed in CAR of same sessions was not significantly different among three groups. The memory process of these young rats also was not affected significantly by two types of diets. Under the light of our results one can suggest that, in the case of alterations in antioxidant defense status, the learning and the memory mechanisms seems to be not affected. Further researches are needed to be able to explain the possible role of oxidative stress on the mechanisms of learning and memory.     

Effects of special brain area regional cerebral blood flow abnormal perfusion on learning and memory function and its molecular mechanism in rats

s To study the effect of special brain area regional cerebral blood flow (rCBF) abnormal perfusion on learning and memory function and its molecular mechanism,64 adult male healthy Spragne-Dawley (SD) rats were randomly divided into two groups,the false operation group (control group) and the operation group (model group).After surgical operation,the operation group undertook bilateral common carotid artery permanent ligation,while the other group did not.Learning and memory function were measured by Y-maze at 4 h,8 h,24 h and 3 d after surgical operation,respectively.The rCBF of the right frontal lobe and hippocampus was also detected by the PerifluxPF model laser Doppler flowmetry,and the expressions of c-fos or c-jun or Bcl-2 and Bax were also measured by immune histochemistry S-P method accordingly.Results showed that the rCBF of the right frontal lobe and hippocampus in the operation group was significantly lower than that in the false operation group (P ＜ 0.05).The learning indexes,error number (EN),day of reach standard and total reaction time (TRT) in the operation group,were significantly higher than that in the false operation group (P＜ 0.05).However,the initiative evasion rate in the operation group was significantly lower than that in the false operation group.The study also found that the rCBF was relatively more,the indexes (EN,the day of reach standard and TRT) relatively fewer,but the initiative evasion rate and the memory keeping rate were relatively more.The positive expression and the average absorbency of Fos and Jun in the operation group were significantly higher than that in the false operation group (P＜ 0.05).Furthermore,Bax and Bcl-2 positive cells were all increased over time in the operation group,and the expression ratio of Bax/Bcl-2 in the operation group was significantly higher than that in the false operation group (P＜0.01).In conclusion,rCBF decrease can impair the learning and memory function in rats,which may be related to the increase of the expression ratio of c-fos or c-jun or Bcl-2 or Bax in the frontal cortex and hippocampus.     

The effect of intrahippocampal injection of kainic acid on corticosterone release in rats

The aim of the present study was to investigate whether the hiopocampus exerts a modulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Kainic acid was stereotaxically injected into the CA1 pyramidal cell layer of the dorsal hippocampus, causing histological and behavioural changes typical of kainic acid toxicity. The CA3 pyramidal cells of the dorsal hippocampus were selectively lesioned. Rats treated with kainic acid were hyperactive, executed clockwise rotatory movements and displayed epileptic seizures. The acute excitatory effect of kainic acid on glutamatergic receptors in the hippocampus resulted in an elevation in plasma corticosterone levels, suggesting a stimulation of HPA axis activity. Direct or indirect stimulation of the CA1 pyramidal cells of the dorsal hippocampus appeared to have caused the increase in corticosterone secretion.     

胰岛素对AD模型大鼠空间学习记忆能力的影响

目的:探讨胰岛素对阿尔茨海默氏病(AD)模型大鼠学习记忆能力影响及其可能机制。方法:大鼠海马微量注射Okadaic acid(OA),胰岛素侧脑室注射。水迷宫实验检测大鼠学习记忆能力;Western blotting实验检测大鼠海马烟碱型胆碱能受体的表达;免疫组化观察大鼠脑内胶质纤维酸性蛋白(GFAP)的表达。结果:与对照组比较,模型组大鼠学习记忆能力明显下降(P<0.01),烟碱型胆碱能受体表达减少(P<0.05),GFAP免疫阳性星形胶质细胞增多(P<0.05)。与模型组相比,胰岛素组大鼠学习记忆能力明显提高(P<0.01),烟碱型胆碱能受体表达增多(P<0.05),GFAP免疫阳性星形胶质细胞减少(P<0.05)。结论:胰岛素提高AD模型大鼠的学习记忆能力可能与其改善模型鼠胆碱能系统功能及减少星形胶质细胞增生有关。     

全脑缺血模型中不同缺血时间参数对预处理保护效应的影响

目的：观察脑缺血预处理（CIP）的持续时间、CIP与后续损伤性缺血之间的间隔时间对CIP抗全脑缺血所致海马锥体神经元迟发性死亡（DND）作用的影响。方法：采用四血管闭塞法（4VO）,制作大鼠全脑缺血模型。脑组织切片硫堇染色法观察海马CA1区锥体神经元DND程度,确定组织学分级（HG）。结果：Sham组和3minCIP组海马未见DND。损伤性脑缺血组海马CA1区有明显的DND,其中6min、10min缺血组的HG为2～3级,15min缺血组的HG主要为3级。CIP＋损伤性脑缺血组中,3min-3d-6min（3minCIP后间隔三天给予6min损伤性脑缺血,下同）和3min-3d-10min组DND不明显,提示CIP可有效地保护海马CAl区神经元,防止6min或10min损伤性脑缺血诱导的DND。在3min-1d-10min组和3min-3d-15min组中,CIP的保护效应较3min-3d-10min组明显减弱。定量分析CIP对海马神经元的保护效应发现,3min-3d-6min组的神经元保护数（PN）和保护指数（PI）与3min-3d-10min组相比无明显差别（P〉0．05）;但3min-3d-10min组的神经元增长指数（GI）较3min一3d一6min组明显升高（P〈0．05）。结论：虽然3min-3d-6min组与3min-3d-10min组中CIP对神经元的保护作用相近,但3min-3d-10min组中,CIP的保护作用更容易被观察到,且CIP的保护潜能可得到最大程度的显现。应用3min-3d-10min组的时间参数建立全脑缺血耐受模型可以诱导出CIP最大的保护潜能。     

学习记忆对脑内c-fos基因表达的影响

学习记忆是人和动物重要的脑功能，大量事实表明，学习记忆过程与脑内ｃ－ｆｏｓ基因的表达密切相关。由学习记忆所诱导的ｃ－ｆｏｓ基因表达在脑内广泛分布，以皮层、海马和边缘系统为多，依学习记忆训练模型的不同，其表达时程有所差异，但一般于训练后立即或３０分钟左右出现，１～２小时左右达峰值。被动和主动回避训练、光辨别训练及味觉厌恶性条件反射训练等多种学习记忆模型均可诱导脑内ｃ－ｆｏｓ基因的表达。其他影响学习记     

Effect of glutamate and riluzole on manganese-induced apoptotic cell signaling in neuronally differentiated mouse P19 Cells

Excess exposure to Mn causes a neurological disorder known as manganism which is similar to dystonic movements associated with Parkinson's disease. Manganism is largely restricted to occupations in which high atmospheric levels are prevalent which include Mn miners, welders and those employed in the ferroalloy processing or related industrial settings. T1 weighted MRI images reveal that Mn is deposited to the greatest extent in the globus pallidus, an area of the brain that is presumed to be responsible for the major CNS associated symptoms. Neurons within the globus pallidus receive glutamatergic input from the subthalamic nuclei which has been suggested to be involved in the toxic actions of Mn. The neurotoxic actions of Mn and glutamate are similar in that they both affect calcium accumulation in the mitochondria leading to apoptotic cell death. In this paper, we demonstrate that the combination of Mn and glutamate potentiates toxicity of neuronally differentiated P19 cells over that observed with either agent alone. Apoptotic signals ROS, caspase 3 and JNK were increased in an additive fashion when the two neurotoxins were combined. The anti-glutamatergic drug, riluzole, was shown to attenuate these apoptotic signals and prevent P19 cell death. Results of this study confirm, for the first time, that Mn toxicity is potentiated in the presence of glutamate and that riluzole is an effective antioxidant which protects against both Mn and glutamate toxicity.     

强制运动促进成年大鼠海马齿状回神经发生并提高学习能力

为了探讨强制运动对成年大鼠海马齿状回（dentate gyrus,DG）神经发生的影响,强制大鼠在马达驱动的转轮中跑步,用5-溴-2-脱氧尿苷（5-bromo-2-deoxyuridine,BrdU）标记增殖细胞,巢蛋白（neuroepthelial stem cell protein,nestin）标记神经干细胞／前体细胞,然后用免疫细胞化学技术检测大鼠DG中BrdU及nestin阳性细胞。为了解强制运动后DG增殖细胞的功能意义,采用Y-迷宫检测大鼠的学习能力。结果表明,强制运动组DG中BrdU及nestin阳性细胞数均日月显多于对照组（P〈0．05）：强制运动对DG神经发生的效应有强度依赖性。Y-迷宫检测结果显示,强制运动能明显改善大鼠的学习能力。结果提示,在转轮中进行强制跑步能促进成年火鼠DG的神经发生,并改善学习能力。     

嗜酸乳杆菌MG2_1对大鼠血清脂质代谢的影响研究

利用从蒙古国酸马奶中分离鉴定,并通过耐酸性及体外降胆固醇能力测试筛选获得的L.acidophilusMG2_1菌制备成活菌体和热致死菌体制剂与高脂饲料同时灌喂Wistar系大鼠,研究探讨了对其血清脂质代谢的影响。结果显示,试验第14天时菌活菌体组和热致死菌体组与单纯饲喂高脂饲料对照组比较,对大鼠血清胆固醇浓度的上升分别呈现显著(p<0.05)和极显著的抑制效果(p<0.01),其热致死菌体组大鼠血清HDL_C,显著高于高脂饲料对照组(p<0.05)。并且各试验组大鼠动脉硬化指数均极显著地低于高脂饲料对照组(p<0.01)。热致死菌体组大鼠粪便中总胆汁酸含量也显著高于高脂饲料组(p<0.05)。可见,该菌株具有一定的抑制大鼠血清胆固醇含量上升和预防动脉硬化的作用。但在整个试验期内不改变灌服菌液剂量的情况下,随着试验时间的延长,该菌株对大鼠血清脂质的影响呈减弱趋势。     

莪术油注射液对慢性低氧大鼠学习与记忆的影响

本文旨在探讨莪术油注射液对慢性低氧大鼠学习与记忆的影响及其可能机制.将Sprague.Dawley大鼠随机分为对照组、慢性低氧组、5 mg/kg体重莪术油组、10 mg/kg体重莪术油组、20 mg/kg体重莪术油组,每组14只.慢性低氧处理采用低氧舱内吸入大约10%O2、5%CO2,饲养10 h/d,持续饲养28 d.莪术油组大鼠低氧处理前腹腔注射相应浓度的莪术油注射液.实验结束次日,通过Morris水迷宫测试各组动物学习和记忆成绩的变化;测定各组大鼠血清和海马组织丙二醛(malonaldehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性以及海马组织Ca2 浓度([Ca2 i]);通过免疫组织化学和Western blot检测磷酸化Ca2 /钙调蛋白依赖性蛋白激酶Ⅱ(phosphorylated Ca2 /calmodulin-dependent pro-tein kinase Ⅱ,p-CaMKII)在海马组织和胞膜上的表达.结果显示,与对照组相比,慢性低氧组大鼠隐蔽平台的逃避潜伏期明显延长(P<0.05),血清和海马组织MDA含量明显增高,SOD活性显著降低(P<0.05,P<0.01),海马组织[Ca2 ]i明显增高(P<0.01),海马P-CaMKII表达量显著降低(P<0.01).与慢性低氧组比较,莪术油各组发生以下变化:10、20 mg/kg体重莪术油组大鼠隐蔽平台的逃避潜伏期显著缩短(P<0.05):5、10、20 mg/kg体重莪术油组大鼠血清和海马组织MDA含量均显著降低(P相似文献   

The effect of case teaching on meaningful and retentive learning when studying genetic engineering

The purpose of this study is to investigate the effects of case teaching on how students learn about genetic engineering, in terms of meaningful learning and retention of learning. The study was designed as quasi-experimental research including 63 8th graders (28 boys and 35 girls). To collect data, genetic engineering achievement tests were developed by the researchers and concept maps (CMs) were used. In the study, the experimental group (n = 31) experienced case teaching, while the comparison group (n = 32) experienced ordinary teaching. To analyse the data from achievement test scores, the Wilcoxon signed-rank test and the Mann–Whitney U test were used. In analysis of the CMs, the number of concepts, number of connecting phrases, number of examples used in the maps and shape of the maps were determined. The analyses showed that the mean achievement scores of the groups significantly differed in favour of the experimental group. Also, retention of the learning in the experimental group was observed. The number of concepts used in CMs did not significantly differ, while the number of connecting phrases in both groups differed significantly in favour of the experimental group. In addition, the students in the experimental group changed their initial hierarchical maps into branched maps, indicating more connection to other concepts.     

慢性间歇低氧对幼鼠脑区p38MAPK的影响

目的：研究慢性间歇低氧对幼鼠部分脑区p38MAPK的影响。方法：SPF级健康雄性SD幼鼠（3-4周龄）50只,随机分为5组（n=10）：间歇低氧2周组（2IH组）、间歇低氧4周组（4IH组）、间歇低氧4周后恢复组（4F组）、对照2周组（2C组）和对照4周组（4C组）。建立慢性间歇低氧幼鼠模型,以RT-PCR法和Westemblot法分别测幼鼠海马及前额叶皮层p38MAPKmRNA和磷酸化p38MAPK（p-p38）蛋白的表达。结果：21H、4IH和4F组幼鼠海马、前额叶皮层的p38MAPK mRNA及p-p38蛋白均明显高于相应对照组（P均〈0．05）。结论：慢性间歇低氧可激活幼鼠部分脑区D38MAPK。     

The effect of learning on experimental evolution of resource preference in Drosophila melanogaster

Abstract Learning is thought to be adaptive in variable environments, whereas constant, predictable environments are supposed to favor unconditional, genetically fixed responses. A dichotomous view of behavior as either learned or innate ignores a potential evolutionary interaction between the learned and innate components of a behavioral response. We addressed this interaction in the context of oviposition substrate choice in Drosophila melanogaster, asking two main questions. First, will learning also evolve in a constant environment in which it always pays to show the same choice? Second, how does an opportunity to learn affect the evolution of the innate (genetic) component of oviposition substrate choice? We exposed experimental populations to four selection regimes, involving selection on oviposition substrate preference (an orange versus a pineapple medium). In two selection regimes the flies were selected for preference either for the orange medium, or for the pineapple medium. In the remaining two selection regimes the flies were also selected for preference for either orange or pineapple, but additionally could use past experience (aversion learning) to decide which medium it paid to avoid. Lines exposed to the latter selection regimes evolved improved learning ability, indicating that learning may be advantageous even if the same behavioral response is favored every generation. Furthermore, of the two selection regimes that favored oviposition on the pineapple medium, the regime that allowed for learning led to the evolution of a stronger innate preference for pineapple, than the regime that did not allow for learning. In contrast, of the two regimes that selected for oviposition on the orange medium, the one that allowed for learning led to a smaller evolutionary change of the innate preference. Thus, an opportunity to learn facilitated the evolution of innate preference under selection for preference for pineapple, but hindered it under selection for preference for orange. We discuss possible mechanisms for this effect.