Hartmann H, Eckert A, Förstl H, Müller W E
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Eur Arch Psychiatry Clin Neurosci. 1994;243(5):218-23. doi: 10.1007/BF02191577.
Several studies suggest that alterations of cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease (AD). However, only few data are presently available giving detailed information about specific characteristics of age-related or AD-specific changes in cellular Ca(2+)-homeostasis. To allow a comprehensive evaluation of age-related changes in [Ca2+]i we performed parallel investigations in central mouse brain cells and mouse spleen lymphocytes of young and aged animals and also in human lymphocytes and granulocytes of young and aged donors and additionally of AD patients. In aged animals, basal [Ca2+]i was decreased in brain cells but increased in spleen lymphocytes. No age-related alterations in baseline [Ca2+]i was found in human lymphocytes or granulocytes. However, comparison of activation-induced rise in [Ca2+]i revealed parallel age-related changes in the different cell-types investigated. The increase in [Ca2+]i after depolarization of mouse brain cells with KCl and after stimulation of mouse lymphocytes with phytohaemagglutinin (PHA) was significantly impaired in aged animals. Moreover, activation of human lymphocytes with PHA also revealed a reduced increase in [Ca2+]i in cells of aged donors. In lymphocytes of AD-patients there was a tendency to higher basal [Ca2+]i compared to their aged matched controls, but no specific alterations in [Ca2+]i could be found after stimulation with PHA. Also no age-related or AD-specific changes were found in granulocytes after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP).(ABSTRACT TRUNCATED AT 250 WORDS)
多项研究表明,胞质游离钙浓度([Ca2+]i)的改变与衰老及阿尔茨海默病(AD)的病理生理学有关。然而,目前仅有少量数据提供有关细胞钙稳态中与年龄相关或AD特异性变化的具体特征的详细信息。为全面评估[Ca2+]i的年龄相关变化,我们对年轻和老年动物的小鼠中枢脑细胞和小鼠脾脏淋巴细胞,以及年轻和老年供体以及AD患者的人淋巴细胞和粒细胞进行了平行研究。在老年动物中,脑细胞的基础[Ca2+]i降低,但脾脏淋巴细胞中的基础[Ca2+]i升高。在人淋巴细胞或粒细胞中未发现基线[Ca2+]i的年龄相关改变。然而,比较激活诱导的[Ca2+]i升高发现,在所研究的不同细胞类型中存在平行的年龄相关变化。用氯化钾使小鼠脑细胞去极化后以及用植物血凝素(PHA)刺激小鼠淋巴细胞后,老年动物中[Ca2+]i的增加明显受损。此外,用PHA激活人淋巴细胞也显示老年供体细胞中[Ca2+]i的增加减少。在AD患者的淋巴细胞中,与年龄匹配的对照组相比,基础[Ca2+]i有升高的趋势,但用PHA刺激后未发现[Ca2+]i的特异性改变。在用N-甲酰甲硫氨酰亮氨酰苯丙氨酸(fMLP)刺激后,粒细胞中也未发现与年龄相关或AD特异性的变化。(摘要截短于250字)