帕罗西汀对皮质酮抑制成年大鼠海马细胞增殖的调制作用

目的慢性糖皮质激素治疗叮能导致认知和情感变化,这或许是由于糖皮质激素对海马神经发牛肢细胞增殖的抑制作用造成。帕罗西汀是一种选择性血清素重摄取抑制剂,临床常用作减轻抑郁症状,近几年来发现它能促进海马神经发生。本研究探讨帕罗西汀与慢性糖皮质激素的相耳作用。方法成年大鼠被分成四绀,分别给予芝麻油、皮质酮、帕罗西汀或皮质酮和帕罗西汀十四天。溴脱氧尿嘧啶核苷（5-bromo-2-deoxyuridine,BrdU）免疫组化法被用于定量齿状回的细胞增殖。结果皮质酮抑制了海马的细胞增殖,帕罗西汀增加了海马的细胞增殖。同时给药组还显示帕罗西汀能逆转皮质酮的抑制作用。结论本研究结果对防止海码在类同醇治疗以后的损害或许有临床意义。     

帕罗西汀对皮质酮抑制成年大鼠海马细胞增殖的调制作用(英文)

目的慢性糖皮质激素治疗可能导致认知和情感变化,这或许是由于糖皮质激素对海马神经发生及细胞增殖的抑制作用造成。帕罗西汀是一种选择性血清素重摄取抑制剂,临床常用作减轻抑郁症状,近几年来发现它能促进海马神经发生。本研究探讨帕罗西汀与慢性糖皮质激素的相互作用。方法成年大鼠被分成四组,分别给予芝麻油、皮质酮、帕罗西汀或皮质酮和帕罗西汀十四天。溴脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,BrdU)免疫组化法被用于定量齿状回的细胞增殖。结果皮质酮抑制了海马的细胞增殖,帕罗西汀增加了海马的细胞增殖。同时给药组还显示帕罗西汀能逆转皮质酮的抑制作用。结论本研究结果对防止海马在类固醇治疗以后的损害或许有临床意义。     

捆绑并倒悬复合刺激大鼠海马CA3区神经肽Y和Nestin的变化

【目的】应用改良的连续、恒定复合型应激大鼠模型,观察其血浆肾素活性（PRA）、血管紧张素Ⅱ（AngⅡ）水平和海马CA3区的Nestin、NPY表达。【方法】将雌性成鼠束缚并倒悬应激6h/d,用放射免疫法测定急性应激(3d)后血浆PRA、AngⅡ水平,用免疫组织化学方法观察应激3d、21d后CA3区锥体层细胞的Nestin、NPY表达变化。【结果】①急性应激组血浆PRA和AngⅡ水平比正常对照组显著降低（P<0.01）,尤其是PRA水平的变化最明显。②急、慢性应激组海马CA3区的Nestin、NPY免疫阳性反应产物总面积（SA）和体视学光密度（IOD）值均较对照组低（P<0.01）,急性组的组织损害比慢性组更严重。【结论】本研究成功地构建了具有科学理论依据和实用价值的复合性应激大鼠模型,并利用此模型研究证实应激早期大鼠血浆PRA水平的降低;以及急、慢性应激大鼠的NPY、Nestin和NF200表达变化及其变化规律,结果提示NPY及其水解产物在应激所致海马神经元细胞骨架损害和谷氨酸释放过程中可能产生一定的影响。     

有氧训练对阿尔茨海默病模型大鼠海马齿状回神经发生的影响

目的：观察有氧训练对β淀粉样蛋白25-35（Aβ25-35）诱导的阿尔茨海默病（AD）大鼠齿状回（DG）神经发生的影响。方法：SD大鼠48只,随机分为假手术组（侧脑室注射生理盐水）,有氧训练组（侧脑室注射Aβ25-35＋4周有氧训练）和实验组（侧脑室注射Aβ25-35）。3组大鼠行Morris水迷宫行为学检测,免疫组织化学方法检测海马DGBrdU阳性细胞数,以确定有氧训练对细胞存活的影响;微管相关蛋白免疫组化染色观察新生神经元的突起生长。结果：①与假手术组比,实验组逃避潜伏期显著延长（P〈0.05）;有氧训练组与实验组比,逃避潜伏期明显缩短（P〈0.05）;有氧训练组逃避潜伏期与假手术组比,差异无统计学意义。②与假手术组比,实验组DGBrdU阳性细胞数显著减少（P〈0.05）。③与假手术组比,实验组DG新生神经元突起的数量明显减少（P〈0.05）。④与实验组比,有氧训练可改善DGBrdU阳性细胞的显著减少（P〈0.05）、保护神经元突起的生长（P〈0.05）。结论：Aβ25-35能诱导AD大鼠模型的建立,损害新生神经元突起生长和新生神经元的存活;有氧训练可改善Aβ25-35损害的大鼠新生神经元突起生长和新生神经元的存活。     

电针对实验性癫痫大鼠海马神经元发生的影响

目的研究电针对实验性癫痫(EP)大鼠海马神经元发生的影响,探讨针刺抗癫痫的机制,为临床实践服务。方法以锂-匹罗卡品制备癫痫模型,电针督脉穴位“大椎”与“百会”,采用疏密波,频率为80Hz,电流强度50mA,时间20min。在6d,13d,27d三个时间点分别腹腔注射2次BrdU,每次间隔2h。所有动物均在最后一次注射BrdU后的24h经左心室灌注处死。取脑后,将脑组织入4%多聚甲醛后固定过夜,再入20%蔗糖4℃冰箱沉底。选择海马部位应用恒冷冰冻切片机冠状位连续切片,脑片漂片厚30μm,行免疫细胞化学染色。结果从13d开始,与未经电针处理的EP鼠比较,经电针处理后的EP鼠海马BrdU阳性细胞数明显减少,且差别有显著性意义(P<0.05)。另外,两组间的反复自发性痫性发作(SRSS)次数亦有显著性差异(P<0.05),经电针处理的EP鼠SRSS次数减少。结论电针可减少SRSS次数并抑制神经元的发生。推测电针的抑痫作用是通过抑制SE后的SRSS而减少神经元的发生。     

大鼠脑缺血再灌注损伤后不同部位神经细胞Nestin的表达

目的研究大鼠脑缺血再灌注损伤后神经细胞巢蛋白（Nestin）的表达，为神经干细胞治疗脑损伤提供理论依据。方法成年健康雄性SD大鼠30只，随机分为实验组和对照组。线栓法建立大脑中动脉闭塞再灌注模型，应用免疫组化SABC法观察2组再灌注后各观察部位不同时间Nestin的表达情况。结果缺血再灌注6h Nestin阳性细胞少量表达；1d时数量增多；3d时明显增多，7d时变化最为显著；各实验组与对照组比较差别均极显著。结论Nestin阳性细胞在正常成年脑组织中广泛表达，损伤后各部位Nestin阳性细胞的表达呈一致性增强，各部位阳性细胞数的增加量在不同时间又有所不同。     

反义Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响

目的探讨Noggin基因对成年大鼠海马内Nestin及GFAP表达的影响。方法反义寡核苷酸技术封闭内源性Noggin基因的表达,免疫组化法检测成年大鼠海马内Nestin与GFAP的表达。结果侧脑室连续4d注射Noggin基因的反义寡核苷酸后,可见海马齿状回(dentate gyrus,DG)内Nestin阳性细胞数与GFAP阳性细胞数较对照组显著增加;室下区GFAP阳性细胞数亦明显增加。结论Noggin对成年海马干细胞的分化有重要作用,内源性Noggin基因的表达可使神经干细胞向神经元方向分化。     

卡马西平对成年癫大鼠海马齿状回BrdU/NeuN表达水平及其对空间记忆的影响

目的研究卡马西平对成年癫大鼠海马齿状回新生神经元的影响及其与空间记忆之间的关系。方法采用氯化锂和匹罗卡品联合诱导大鼠癫模型,利用5-溴脱氧尿苷嘧啶与神经元核性蛋白双标记观察海马齿状回内源性神经前体细胞分化为成熟神经元的情况;利用行为学分析评价大鼠的空间记忆。结果 (1)卡马西平可增加癫大鼠海马齿状回新生成熟神经元的数量(P<0.05);(2)卡马西平对癫大鼠的空间记忆有明显改善作用(P<0.01)。结论卡马西平增加癫大鼠海马齿状回新生成熟神经元形成,是其改善癫大鼠空间记忆的可能机制之一。     

Effect of Prenatal Protein Deprivation on Postnatal Granule Cell Generation in the Hippocampal Dentate Gyrus

The effect of prenatal malnutrition, produced by protein deprivation, on postnatal neurogenesis of granule cells in the fascia dentata of the rat hippocampal formation was examined by injecting tritiated thymidine on P8 and P15 and sacrificing the pups on P30, or by injecting on P30 and sacrificing on P90. The number of labeled granule cells was significantly decreased in prenatally malnourished rats injected on P8, and unaffected in those injected on P15. In contrast, the number of labeled granule cells in prenatally malnourished rats was significantly increased in animals injected on P30. The study shows that prenatal malnutrition significantly alters the postnatal pattern of granule cell neurogenesis in rat hippocampal formation and that the effect persists despite nutritional rehabilitation at birth. Copyright © 1996 Elsevier Science Inc.     

Blockade of Hippocampal Long-Term Potentiation Following Soman Pretreatment in the Rat

One of the most potent toxins known is the cholinesterase inhibitor, soman, which produces severe convulsions and cell loss in the central nervous system. In these experiments the effect of multiple low doses of soman on the acquisition and maintenance of long-term potentiation (LTP) was determined in rats. LTP is a form of synaptic plasticity that has been studied as a cellular substrate for learning and memory mechanisms. Under urethane anesthesia, electrodes were positioned in the dentate gyrus for recording evoked potentials before and after tetanic stimulation of the perforant path. LTP levels were greatly reduced in rats recovering from convulsion-inducing soman treatment. Rats exposed to similar amounts of soman, but not displaying convulsions, also displayed reduced levels of LTP. The responses recorded from these animals were highly variable, ranging from control levels of potentiation to no LTP. The variability could be attributed to some animals having convulsions that were not detected before surgery or to other interanimal differences in the degree of soman-induced toxicity. The long range goal of the experiments presented here is to develop a better rodent model for studying soman-induced functional changes in the CNS that can be detected prior to the gross morphological changes.     

Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats

Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague–Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal ketamine exposure.     

Study of Molecular and Granular Layer of Dentate Gyrus of Female Rats Neonatally Treated with Estrogen

The proliferation of hippocampal dentate gyrus granule cells was investigated using ³H-thymidine incorporation in control and estrogen-treated rats. Newborn 3-day old female Wistar rats were treated with a single dose of 1 mg of estradiol and 30 μCi ³H-thymidine, and were sacrificed when 10 days old. The total number of neurons and the number of labeled granule cells in the granular layer and its subdivisions of both suprapyramidal and infrapyramidal limbs were analyzed using a stereological method. In both limbs, the total number of neurons as well as the total number of labeled granule cells in the granular layer were significantly increased in treated rats compared to corresponding controls. The thicknesses of the molecular and the granular layers and their subdivisions of both suprapyramidal and infrapyramidal limbs were analyzed using a stereological method. In treated female rats the molecular layer (ML) in both limbs was significantly decreased, and the granular layer (GL) was significantly increased in suprapyramidal limb. However, in the infrapyramidal limb an increased number of labeled cells in treated animals were significant in all particular zones of the granular layer. In the suprapyramidal limb's granular layer a significant increase in labeled cells was observed in subgranular zone (SGZ). Our results suggest a differential effect of estradiol on thicknesses of the ML and the GL, and dentate gyrus granule cells proliferation through the early rat life.     

Effect of colchicine-induced cell loss in the dentate gyrus and Ammon's horn on the olfactory control of feeding in rats

Normal rats offered a choice between scented and unscented food pellets: (a) avoid food scented with toluene (an aromatic organic solvent) or 2-propylthietane (a component of the anal scent gland secretions of weasels); (b) prefer food scented with cadaverine (a diamine component of the odor of rotting flesh); but (c) neither prefer nor avoid food scented with butyric acid (a component of the odor of rancid butter) or caproic acid (a component of the odor of goats). Lesions of the dentate gyrus and CA1 (induced by local injections of colchicine) and/or the neocortex overlying the hippocampus produce a complex pattern of changes in these normal olfactory reactions, but do not affect the normal reaction to food flavored with sucrose or quinine. Cell loss in the hippocampal formation results in an abnormal aversion to butyric acid, in particular, but neocortical damage also alters the behavioral reaction to scented food. The results are consistent with the view that the hippocampal formation and the neocortex play differing roles in the olfactory control of behavior.     

GIRK1在颞叶癫痫大鼠海马齿状回中的表达及其意义

目的探讨GIRK1在颞叶癫癎大鼠海马齿状回的表达及其意义.方法112只雄性SD大鼠随机分为实验组(n=70)与对照组(n=42),同时建立海人藻酸(KA)颞叶癫模型.选取KA腹腔注射后3、6、12、24、48 h,7、30 d为研究的时间点.用原位杂交法及免疫组织化学法检测海马齿状回GIRK1 mRNA及蛋白的表达.结果实验组大鼠海马齿状回GIRK1 mRNA表达在致癎后6 h较对照组减少,而在致癎后至7～30 d较对照组增高.结论在颞叶癫癎的不同时期海马齿状回GIRK1表达的变化反映出颞叶癫癎的复杂性.