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作 者:高静[1] 吴娟[1] 赵晓宁[1] 张维宁[1] 张毅奕 张祖暄[1]
机构地区:[1]南京大学医学院
出 处:《生理学报》1994年第1期44-51,共8页Acta Physiologica Sinica
基 金:国家自然科学基金;南京大学现代分析中心测试基金
摘 要:3-Glu示踪实验表明,谷氨酸可以透过胎盘屏障进入胎鼠体内,较均一地分布于中枢神经系统及内脏各器官。给母鼠隔日注射高、低剂量的谷氨酸单钠(MSG,2.5ms/g,1.0mg/g)至分娩,对成年后的仔鼠进行检测发现,高剂量组仔鼠记忆能力及Y-迷宫空间分辨学习能力均严重受损,下丘脑弓状核及腹内侧核神经元被明显破坏,出现胞质肿胀、核固缩、神经元数目减少。孕期MSG处理还可以使仔鼠下丘脑和海马3H-Glu受体-配体结合量显著变化。采用AR-CM-MIC阳离子检测系统观察单个神经元内游离Ca2+浓度([Ca2+]i)的变化时还发现,MSG可以通过诱发胞外Ca2+内流及胞内钙库释放Ca2+来增高[Ca2+]i。以上结果提示:MSG对仔鼠的剂量依赖性神经毒性作用可能与其过度激活膜谷氨酸受体,引起细胞内Ca2+超载,最终导致特定脑区的神经元发生溃变甚至死亡有关,而这些变化可能正是仔鼠成年后学习记忆受损的原因。Monosodium glutumate(MSG) was shown to penetrate placental barrier and distribute almost evenly among embryonic tissues using 3H-Gln as a tracer. When a lower(1. 0 mg/g) and a higher(2. 5 mg/g) doses of MSG were alternatively injected to Kunming maternal mice in every other days from mating to deliveries, obvious injury Occured in the ability of memory retention and y-maze discrimination learning of adult filial mice pregnantly treated with higher doses(2. 5 mg/g) of MSG. Meanwhile, the neuronal damages were observed in not only arcuate nucleus but also ventromedial nucleus of hypothalamus. Characteristic cytopathalogical changes induced by MSG showed swollon cytoplasm, dark pyknotic nuclei and loss of neurons. The radioligandbindings in both hippocampus and hypothalamus altered significantly after the pregnant treatment of MSG. Possible mechanisms underlying MSG excitotoxic phenomena studied in single neuron by use of Ca2+ sensitive indicator Fura-2 with Spex AR-CM-MIC Canon Measurement System, might be dur to increases of intracellular free Ca2+ concentration induced by MSG exposure, which was related to both the influx of Ca2+ and the depletion of Ca2+ from the intracellular Ca2+ stores. These experimental findings in dicated that MSG performed its transplacental neurotoxicity in a dose-dependent manner. The excessive activation of Gin receptors and the overloading of intracellular Ca2+ induced by MSG ultimately leading to neuronal death may result in the reduction of the capability of learning and memory in adult filial mice pregnantly treated with MSG.
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