Summary
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 Ca2+-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-fomyl-methionyl-leucyl-phenylalanine (fMLP). Since K+- and PHA-induced rise in [Ca2+]i is mainly mediated by Ca2+-influx, whereas fMLP-stimulated rise in [Ca2+]i is mainly due to intracellular Ca2+-release, our findings might indicate that age-related disturbances of Ca2+-homeostasis especially affect mechanisms involved in Ca2+-influx. The corresponding age-related alterations in mouse brain cells, mouse spleen lymphocytes and human lymphocytes after cell activation suggest a similar impairment of Ca2+-homeostatis in these cells and might justify the speculation that Ca2+-homeostasis in the aged human brain is affected in a comparable fashion.
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References
Adunsky A, Baram D, Hershkowitz M, Mekori YA (1991) Increased cytosolic calcium in lymphocytes of Alzheimer patients. J Neuroimmunol 33:167–172
Berg L (1984) Clinical dementia rating (Letter) Br J Psychiatry 145:339
Bondy B, Klages U, Müller-Spahn F, Hock C (1994) Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls. Eur Arch Psychiatry Clin Neurosci 243:224–228
Boyum A (1984) Separation of lymphocytes, granulocytes and monocytes from human blood using iodinated density gradient media. Methods Enzymol 108:88–102
Förstl H, Besthorn C, Geiger-Kabisch C, Sattel H, Schreiter-Gasser U (1993) Psychotic features and the course of Alzheimer's disease: relationship to cognitive, EEG and CT-Scan findings. Acta Psychiatr Scand 87:395–399
Franklin RA, Arkins S, Kelley KW (1990) The proliferative response of rat T cells to calcium ionophores increase with age. Cell Immunol 130:416–428
Gibson GE, Peterson C (1987) Calcium and the aging nervous system. Neurobiol Aging 8:319–343
Giovanelli L, Pepeu G (1989) Effect of age on K+-induced cytosolic Ca2+ changes in rat cortical synaptosomes. J Neurochem 53:392–398
Grossmann A, Ledbetter JA, Rabinovitch PS (1989) Reduced proliferation of T lymphocytes in aged humans is predominantly in the CD8+ subset and is unrelated to defects in transmembrane signaling which are predominantly in the CD4+ subset. Exp Cell Res 180:367–382
Grossmann A, Maggio-Price L, Jinneman JC, Rabinovitch PS (1991) Influence of aging on intracellular free calcium and proliferation of mouse T-cell subsets from various lymphoid organs. Cell Immunol 135:188–131
Grynkiewiecz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450
Hartmann H, Eckert A, Müller WE (1993) Aging enhances the calcium sensitivity of central neurons of the mouse as an adaptive response to reduced free intracellular calcium. Neurosci Lett 152:181–184
Hartmann H, Müller WE (1993) Age-related changes in receptor-mediated and depolarization-induced phosphatidylinositol turnover in mouse brain. Brain Res 622:86–92
Huang HM, Toral-Barza L, Thaler H, Tofel-Grehl B, Gibson GE (1991) Inositol phosphates and intracellular calcium after bradykinin stimulation in fibroblasts from young, normal aged and Alzheimer donors. Neurobiol Aging 12:469–473
Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3:645–653
Khachaturian ZS (1989) The role of calcium regulation in brain aging: reexamination of a hypothesis. Aging 1:17–34
Leslie SW, Chandler LJ, Barr EM, Farrar RP (1985) Reduced calcium uptake by rat brain mitochondria and synaptosomes in response to aging. Brain Res 329:177–183
Lustyik G, O'Leary JJ (1989) Aging and the mobilitation of intracellular calcium by phytohemmagglutinin in human T cells. J Gerontol 44:B30–36
Martinez A, Vitorica J, Bogonez E, Satrustegui J (1987) Differential effects of age on the pathways of calcium influx into nerve terminals. Brain Res 435:249–257
Martinez A, Vitorica J, Satrustegui J (1988) Cytosolic free calcium levels increase with age in rat brain synaptosomes. Neurosci Lett 88:336–342
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: a report of the NINCDS-ADRDA work group under the Anspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 34:939–944
Michaelis ML, Foster CT, Jayawickreme C (1992) Regulation of calcium levels in brain tissue from adult and aged rat. Mech Ageing Dev 62:291–306
Michel MC, VanTits LJH, Trenn G, Sykora J, Brodde OE (1992) Dissociation between phytohemagglutinin-stimulated generation of inositol phosphates in Ca2+-increase in human mononuclear leukocytes. Biochem J 285:137–141
Miller RA, Jacobson B, Weil G, Simons ER (1987) Diminished calcium influx in lectin-stimulated T cells from old mice. J Cell Physiol 132:337–342
Miller RA, Philosophe B, Ginis I, Weil G, Jacobson B (1989) Defective control of cytoplasmic calcium concentration in T lymphocytes from old mice. J Cell Physiol 138:175–182
Peterson C, Gibson GE (1983) Aging and 3,4 diaminopyridine alter synaptosomal calcium uptake. J Biol Chem 258:11482–11486
Peterson C, Ratan RR, Shelanski M, Goldman JE (1986) Cytosolic free calcium and cell spreading decrease in fibroblasts from aged and Alzheimer donors. Proc Natl Acad Sci USA 83: 7999–8001
Stoll L, Schubert T, Müller WE (1991) Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment. Neurobiol Aging 13:39–44
Thompson NT, Bonser RW, Tateson JE, Spacey GD, Randall RW, Hodson HF, Garland LG (1991) A quantitative investigation into the dependence of Ca2+ mobilization on changes in inositol 1,4,5-trisphosphate levels in the stimulated neutrophil. Br J Pharmacol 103:1592–1596
Toth S, Csermely P, Beregi E, Szkladanyi A, Szabo LD (1989) Decreased cytosolic free calcium concentration of aged human lymphocytes in resting state. Compr Gerontol Suppl Issue A+B 3:16–22
Villalba MA, Martinez-Serrano C, Brner P, Blanco P, Satrustegui J (1992) NMDA-induced increase in [Ca2+]i and45Ca2+uptake in acutely dissociated brain cells derived from adult rats. Brain Res 570:347–353
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Hartmann, H., Eckert, A., Förstl, H. et al. Similar age-related changes of free intracellular calcium in lymphocytes and central neurons: Effects of Alzheimer's disease. Eur Arch Psychiatry Clin Nuerosci 243, 218–223 (1994). https://doi.org/10.1007/BF02191577
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DOI: https://doi.org/10.1007/BF02191577