Abstract
A vast number of studies has demonstrated causal relations between excessive elevation of the free intra neuronal calcium concentration ([Ca2+] i ) and neurodegeneration. Calcium-induced neurodegeneration is believed to occur in acute conditions such as nerve-transection induced Wallerian degeneration (Waller, 1850), mechanical brain trauma, brain ischemia, hypoglycemic coma and status epilepticus. Calcium-induced neurodegeneration is also believed to participate in chronic conditions such as Alzheimer’s disease and aging. The degenerative effects of the elevated [Ca2+] i are thought to be mediated by the unbalanced activation of enzymes that take part in the normal neuronal function. These include proteinases, phospholipases, phosphatases and protein kinases. In turn, the unbalanced activation of these enzymes leads to cytoskeletal damage, membrane dysfunction, enhanced production of free radicals and, finally, neuronal degeneration (reviewed in Choi, 1994; Siesjo, 1994; Rothman and Olney, 1995; Kristian and Siesjo, 1998).
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References
Augustine, G.J. and Neher, E., 1992, Calcium requirements for secretion in bovine chromaffin cells, J. Physol. Lond. 450, 247–271.
Aunis, D. and Bader, M.F., 1988, The cytoskeleton as a barrier to exocytosis in secretory cells, J. Exp. Biol. 139, 253–266.
Ballinger, M.L. and Bittner, G.D., 1980, Ultrastructural studies of severed medial giant and other CNS axons in crayfish, Cell Tissue Res. 208, 123–133.
Bednarski, E., Vanderklish, P., Gall, C., Saido, T.C., Bahr, B.A. and Lynch, G., 1995, Translational suppression of calpain I reduces NMDA-induced spectrin proteolysis and pathophysiology in cultured hippocampal slices, Brain Res. 694, 147–157.
Benbassat, D. and Spira, M.E., 1993, Survival of isolated axonal segments in culture: Morphological, ultrastructural, and physiological analysis, Exp. Neurol. 122, 295–310.
Bittner, G.D., 1991, Long-term survival of anucleate axons and its implications for nerve regeneration, Trends Neurosci. 14, 188–193.
Borgens, R.B., Jaffe, L.F. and Cohen, M.J., 1980, Large and persitent electrical currents enter the transected lamprey spinal cord, Proc. Natl. Acad. Sci. USA 11, 1209–1213.
Brorson, J.R., Manzolillo, P.A. and Miller, R.J., 1994, Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells, J. Neurosci. 14, 187–197.
Choi, D.W., 1994, Calcium and excitotoxic neuronal injury, Ann. N.Y. Acad. Sci. 141, 162–171.
del Cerro, S., Arai, A., Kessler, M., Bahr, B.A., Vanderklish, P., Rivera, S. and Lynch, G., 1994, Stimulation of NMDA receptors activates calpain in cultured hippocampal slices, Neurosci. Lett. 167, 149–152.
Faddis, B.T., Hasbani, M.J. and Goldberg, M.P., 1997, Calpain activation contributes to dendritic remodeling after brief excitotoxic injury in vitro, J. Neurosci. 17, 951–959.
Gabso, M., Neher, E. and Spira, M.E., 1997, Low mobility of the Ca2+ buffers in axons of cultured Aplysia neurons, Neuron 18, 473–481.
Gallant, P.E., 1988, Effects of the extarnal ions and metabolic poisoning on the constriction of the squid giant axon after axotomy, J. Neurosci. 8, 1479–1484.
George, E.B., Glass, J.D. and Griffin, J.W., 1995, Axotomy-induced axonal degeneration is mediated by calcium influx through ion-specific channels, J. Neurosci. 15, 6445–6452.
Gitler, D. and Spira, M.E., 1998, Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation, Neuron 20, 1123–1135.
Godell, C.M., Smyers, M.E., Eddleman, C.S., Ballinger, M.L., Fishman, H.M. and Bittner, G.D., 1997, Calpain activity promotes the sealing of severed giant axons, Proc. Natl. Acad. Sci. USA 94, 4751–4756.
Gross, G.W. and Higgins, M.L., 1987, Cytoplasmic damage gradients in dendrites after transection lesions, Exp. Brain Res. 67, 52–60.
Horwitz, S.B., 1994, Taxol (paclitaxel): Mechanisms of action, Ann. Oncol. 5 (Suppl. 6), S3–S6.
Howard, M.J., David, G. and Barrett, J.N., 1999, Resealing of transected myelinated mammalian axons in vivo: Evidence for involvement of calpain, Neuroscience 93, 807–815.
Kandel, E.R., Schwartz, J.H. and Jessell, T.M., 1991, Principles of Neuronal Science, Elsevier, New York.
Kosaka, T., Kosaka, K., Nakayama, T., Hunziker, W. and Heizmann, C.W., 1993, Axons and axon terminals of cerebellar Purkinje cells and basket cells have higher levels of parvalbumin immunoreactivity than somata dendrites: Quantitative analysis by immunogold labeling, Exp. Brain Res. 93, 483–491.
Kristian, T. and Siesjo, B.K., 1998, Calcium in ischemic cell death, Stroke 29, 705–718.
Leytus, S.P., Melhado, L.L. and Mangel, W.F., 1983a, Rhodamine-based compounds as fluorogenic substrates for serine proteinases, Biochem. J. 209, 299–307.
Leytus, S.P., Patterson, W.L. and Mangel, W.F., 1983b, New class of sensitive and selective fluorogenic substrates for serine proteinases. Amino acid and dipeptide derivatives of rhodamine, Biochem. J. 215, 253–260.
Llinas, R., Sugimori, M. and Silver, R.B., 1992, Microdomains of high calcium concentration in a presynaptic terminal, Science 256, 677–679.
Lynch, G. and Baudry, M., 1984, The biochemistry of memory: A new and specific hypothesis, Science 224, 1057–1063.
Lynch, G., Kessler, M., Arai, A. and Larson, J., 1990, The nature and causes of hippocampal long-term potentiation, Prog. Brain Res. 83, 233–250.
Neher, E., 1995, The use of fura-2 for estimating Ca buffers and Ca fluxes, Neuropharmacology 34, 1423–1442.
Perrin, D., Moller, K., Hanke, K. and Soling, H.D., 1992, cAMP and Ca(2+)-mediated secretion in parotid acinar cells is associated with reversible changes in the organization of the cytoskeleton, J. Cell Biol. 116, 127–134.
Roberts, W.M., 1993, Spatial calcium buffering in saccular hair cells, Nature 363, 74–76.
Rothman, S.M. and Olney, J.W., 1995, Excitotoxicity and the NMDA receptor — Still lethal after eight years, Trends Neurosci. 18, 57–58.
Saido, T.C., Sorimachi, H. and Suzuki, K., 1994, Calpain: New perspectives in molecular diversity and physiological-pathological involvement, FASEB J. 8, 814–822.
Seubert, P., Larson, J., Oliver, M., Jung, M.W., Baudry, M. and Lynch, G., 1988, Stimulation of NMDA receptors induces proteolysis of spectrin in hippocampus, Brain Res. 460, 189–194.
Siesjo, B.K., 1994, Calcium-mediated processes in neuronal degeneration, Ann. N.Y. Acad. Sci. 747, 140–161.
Spira, M.E., Benbassat, D. and Dormann, A., 1993, Resealing of the proximal and distal cut ends of transected axons: Electrophysiological and ultrastructural analysis, J. Neurobiol. 24, 300–316.
Strautman, A.F., Cork, R.J. and Robinson, K.R., 1990, The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields, J. Neurosci. 10, 3564–3575.
Vanderklish, P., Saido, T.C., Gall, C., Arai, A. and Lynch, G., 1995, Proteolysis of spectrin by calpain accompanies theta-burst stimulation in cultured hippocampal slices, Brain Res. Mol. Brain Res. 32, 25–35.
Waller, A.V., 1850, Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog and observations of the alterations produced thereby in the structure of their primitive fibres, Philos. Trans. Roy. Soc. Lond. (Biol.) 140, 423–429.
Wang, K.K. and Yuen, P.W., 1994, Calpain inhibition: An overview of its therapeutic potential, Trends Pharmacol. Sci. 15, 412–419.
Xie, X.Y. and Barrett, J.N., 1991, Membrane resealing in cultured rat septal neurons after neurite transection: Evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly, J. Neurosci. 11, 3257–3267.
Yawo, H. and Kuno, M., 1983, How a nerve fiber repairs its cut end: Involvement of phospholipase A2, Science 222, 1351–1353.
Yawo, H. and Kuno, M., 1985, Calcium dependence of membrane sealing at the cut end of the cockroach giant axon, J. Neurosci. 5, 1626–1632.
Ziv, N.E. and Spira, M.E., 1993, Spatiotemporal distribution of Ca2+ following axotomy and throughout the recovery process of cultured Aplysia neurons, Eur. J. Neurosci. 5, 657–668.
Ziv, N.E. and Spira, M.E., 1995, Axotomy induces a transient and localized elevation of the free intracellular calcium concentration to the millimolar range, J. Neurophysol. 74, 2625–2637.
Ziv, N.E. and Spira, M.E., 1997, Localized and transient elevations of intracellular Ca2+ induce the dedifferentiation of axonal segments into growth cones, J. Neurosci. 17, 3568–3579.
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Spira, M.E., Ziv, N.E., Oren, R., Dormann, A., Gitler, D. (2000). High Calcium Concentrations, Calpain Activation and Cytoskeleton Remodeling in Neuronal Regeneration after Axotomy. In: Pochet, R., Donato, R., Haiech, J., Heizmann, C., Gerke, V. (eds) Calcium: The Molecular Basis of Calcium Action in Biology and Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0688-0_34
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