Abstract
The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases.
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References
Menzies FM, Ince PG, Shaw PJ (2002) Mitochondrial involvement in amyotrophic lateral sclerosis. Neurochem Int 40:543–551
Cassarino DS, Bennett JP (1999) An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res Rev 29:1–25
Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res. Rev 25:335–358
Carri MT, Ferri A, Cozzolino M, Calabrese L, Rotilio G (2003) Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Brain Res Bull 61:365–374
Carri MT, Ferri A, Battistoni A, Famhy L, Gabbianelli R, Poccia F, Rotilio G (1997) Exspression of a Cu, Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Lett 414:365–368
Kruman II, Pedersen WA, Springer JE, Mattson MP (1999) ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanisms involving increased oxidative stress and perturbed calcium homeostasis. Exp Neurol 160:28–39
Orrell RW (2000) Amyotrophic lateral sclerosis: copper/zinc superoxide dismutase (SOD1) gene mutations. Neuromuscular Dis 10:63–68
Mitchell JD (2000) Amyotrophic lateral sclerosis: toxins and environment Amyotroph. Lateral Scler Other Motor Neuron Disord 1(4):235–250
Campbell A, Smith MA, Sayre LM, Bondy SC, Perry G (2001) Mechanisms by which metals promote events connected to neurodegenerative diseases. Brain Res Bull 55/2:125–132
Waggoner DJ, Bartnikas TB, Gitlin JD (1999) The role of copper in neurodegenerative disease. Neurobiol Dis 6:221–230
Bush AI (2000) Metals and neuroscience. Curr Op Chem Biol 4:184–191
Hasnain SS (2004) Synchrotron techniques for metalloproteins and human disease in post genome era. J Synchrotron Radit 1:7–11
Carri MT, Battistoni A, Ferri A (1994) A study of the dual role of copper in superoxide dismutase as antioxidant and pro-oxidant in cellular models of amyotrophic lateral sclerosis. Adv Exp Med Biol 448:205–213
Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344(22):1688–1700
Iida A (2000) Instrumentation for μ-XRF at synchrotron sources. In: Janssens KHA, Adams FCV, Rindby A (eds), Microscopic X-Ray Fluorescence Analysis, John Wiley, Chichester, pp 117–153
Bohic S, Simionovici A, Ortega R, Heymann D, Schroer C, Snigirev A (2001) Synchrotron-induced X-ray microfluorescence on single cells. Nucl Instr Meth B 181(1):728–733(6)
Huang YY, Lu JX, He RG, Zhao LM, Wang ZG, He W, Zhang YX (2001) Study of human bone tumor slice by SRXRF microprobe. Nucl Instrum Meth Phys Res A 467–468:1301–1304
Ortega R, Deves G, Fayard B, Salome M, Susini J (2003) Combination of synchrotron radiation X-ray microprobe and nuclear microprobe for chromium and chromium oxidation states quantitative mapping in single cells. Nucl Instrum Meth Phys Res B 210:325–329
Szczerbowska-Boruchowska M, Lankosz M, Ostachowicz J, Adamek D, Krygowska-Wajs A, Tomik B, Szczudlik A, Simionovici A, Bohic S (2004) Topographic and quantitative microanalysis of human central nervous system tissue using synchrotron radiation. X-ray Spectrom 33(1):3–11
Yoshida S, Ektessabi A, Fujisawa S (2001) XAFS spectroscopy of a single neuron from a patient with Parkinson’s disease. J Synchrotron Radiat 8:998–1000
Ide-Ektessabi A, Kawakami T, Watt F (2004) Distribution and chemical state analysis of iron in the Parkinsonian substantia nigra using synchrotron radiation micro beams. Nucl Instrum Meth Phys Res B 213:590–594
Ishihara R, Ide-Ektessabi A, Ikeda K, Mizuno Y, Fujisawa S, Takeuchi T, Ohta T (2002) Investigation of cellular metallic elements in single neurons of human brain tissues. Neuroreport 13(14):1817–1820
Chwiej J, Szczerbowska-Boruchowska M, Wojcik S, Lankosz M, Chlebda M, Adamek D, Tomik B, Setkowicz Z, Falkenberg G, Stegowski Z, Szczudlik A (2005) Implementation of X-ray fluorescence microscopy for investigation of elemental abnormalities in central nervous system tissue. J Alloy Compd 401(1–2):184–188
Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl.):96–107
Falkenberg G, Rickers K (2002) Pink-beam and monochromatic micro-X-ray fluorescence analysis at the beamline L. In: Krell U, Schneider JR, von Zimmerman M (Eds) Hasylab Annual Report 2002 Part I, HASYLAB at DESY, Hamburg, pp 88–95
Simionovici AS, Chukalina M, Schroer CG, Drakopoulos M, Snigirev AA, Snigireva II, Lengeler B, Janssens K, Adams F (2000) High-resolution X-ray fluorescence microtomography of homogeneous samples. IEEE Trans Nucl Sci 47:2736–2740
Bilderback DH, Hoffman SA, Thiel DJ (1994) Nanometer spatial-resolution achieved in hard X-ray-imaging and Laue diffraction experiments. Science 263:201–203
Lengeler B, Schroer CG, Tuemmler J, Benner B, Richwin M, Snigirev A, Snigireva I, Drakopoulos M (1999) Imaging by parabolic refractive lenses in the hard X-ray range. J Synchrotron Radiat 6:1153–1167
Currie LA (1968) Limits for qualitative detection and quantitative determination. Anal Chem 40:586–593
Kapaki E, Zournas C, Kanias G, Zambelis T, Kakami A, Papageorgiou C (1997) Essential trace element alterations in amyotrophic lateral sclerosis. J Neurol Sci 147(2):171–175
Lin DD, Cohen AS, Coulter DA (2001) Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor responses in hippocampal CA3 neurons. J Neurophysiol 85(3):1185–1196
Choi DW, Koh JY (1998) Zinc and brain injury. Ann Rev Neurosci 21:347–375
Frederickson CJ, Koh JY, Bush AJ (2005) The neurobiology of zinc in health and disease. Nat Rev Neurosci 6:449–462
Eom SJ, Kim EY, Lee JE, Kang HJ, Shim J, Kim SU, Gwag BJ, Choi EJ (2001) Zn(2+) induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-Kinase. Mol Pharmacol 59(5):981–986
Mann DMA, Yates PO (1974) Lipoprotein pigments – their relationship to ageing in the human nervous system II. The melanin content of pigmented nerve cells. Brain 97:489–498
Weiss JH, Sensi SL (2000) Ca2+ permeable AMPA/kainate channels and selective neurodegeneration. Trends Neurosci 23:365–371
Frederickson CJ (1989) Neurobiology of zinc and zinc-containingneurons. Int Rev Neurobiol 31:145–238
Coleman JE (1992) Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. Ann Rev Biochem 61:897–946
Estevez AG, Crow JP, Sampson JB, Reiter C, Zhuang Y, Richardson GJ, Tarpey MM, Barbeito L, Beckman JS (1999) Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286:2498–2500
Rotilio G, Carri MT, Rossi L, Ciriolo MR (2000) Copper-dependent oxidative stress and neurodegeneration. IUBMB Life 50(4–5):309–314
Silahtaroglu AN, Brondum-Nielsen K, Gredal O, Werdelin L, Panas M, Petersen MB, Tommerup N, Tümer Z (2002) Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS). BMC Genet 3(1):5
Linder MC (2001) Copper and genomic stability. Mutation Res 475:141–152
Ross BM, Moszczynska A, Ehrlich J, Kish SJ (1998) Low activity of key phospholipid catabolic and anabolic enzymes in human substantia nigra: possible implications for Parkinson’s disease. Neuroscience 83:791–798
Siesjo BK (1981) Cell damage in the brain: A speculative synthesis. J Cereb Blood Flow Metab 1:155–185
Kristian T, Siesjo BK (1996) Calcium related damage in ischemia. Life Sci 59:357–367
Yu SP, Canzoniero LMT, Choi DW (2001) Iron homeostasis and apoptosis. Curr Opin Cell Biol 13:405–411
Bergomi M, Vinceti M, Nacci G, Pietrini V, Bratter P, Alber D, Ferrari A, Vescovi L, Guidetti D, Sola P, Malagu S, Aramini C, Vivoli G (2002) Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study. Environ Res 89(2):116–123
Nagano S, Satoh M, Sumi H (2001) Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose-dependent manner. Eur J Neurosci 13(7):1363–1370
Shaw IC, Fitzmaurice PS, Mitchell JD, Lynch PG (1995) Studies on cellular free radical protection mechanisms in the anterior horn from patients with amyotrophic lateral sclerosis. Neurodegeneration 4(4):391–396
Tomblyn M, Kasarskis EJ, Xu Y, St Clair DK (1998) Distribution of MnSOD polymorphisms in sporadic ALS patients. J Mol Neurosci 10(1):65–66
Liu Y, Brooks BR, Taniguchi N, Hartmann HA (1998) CuZnSOD and MnSOD immunoreactivity in brain stem motor neurons from amyotrophic lateral sclerosis patients. Acta Neuropathol (Berl) 95(1):63–70
Pamphlett R, McQuilty R, Zarkos K (2001) Blood levels of toxic and essential metals in motor neuron disease. Neurotoxicology 22(3):401–410
Kanias GD, Kapaki E (1997) Trace elements, age, and sex in amyotrophic lateral sclerosis disease. Biol Trace Elem Res 56(2):187–201
Kurlander HM, Patten BM (1979) Metals in spinal cord tissue of patients dying of motor neuron disease. Ann Neurol 6(1):21–24
Khare SS, Ehmann WD, Kasarskis EJ, Markesbery WR (1990) Trace element imbalances in amyotrophic lateral sclerosis. Neurotoxicology 11(3):521–532
Markesbery WR, Ehmann WD, Candy JM (1995) Neutron activation analysis of trace elements in motor neuron disease spinal cord. Neurodegeneration 4(4):383–390
Torsdottir G, Kristinsson J, Gudmundsson G, Snaedal J, Johannesson T (2000) Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis. Pharmacol. Toxicol. 87(3):126–130
Kasarskis EJ, Tandon L, Lovell MA, Ehmann WD (1995) Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study. J Neurol Sci 130(2):203–208
Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208
Ince PG, Shaw PJ, Candy JM, Mantle D, Ehmann W, Markesbury W (1994) Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease. Neurosci Lett 182(1):87–90
Nagata H, Miyata S, Nakamura S, Kameyama M, Katsui Y (1985) Heavy metal concentrations in blood cells in patients with amyotrophic lateral sclerosis. J Neurol Sci 67(2):173–178
Kihira T, Mukoyama M, Ando K, Yase Y, Yasui M (1990) Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy. J Neurol Sci 98(2–3):251–258
Ejima A, Watanabe C, Koyama H, Satoh H (1996) Analysis of trace elements in the central nerve tissues with inductively coupled plasma-mass spectrometry. Tohoku J Exp Med 178(1):1–10
Miyata S, Nakamura S, Nagata H, Kameyama M (1983) Increased manganese level in spinal cords of amyotrophic lateral sclerosis determined by radiochemical neutron activation analysis. J Neurol Sci 61(2):283–293
Mitchell JD, East BW, Harris IA (1986) Trace elements in the spinal cord and other tissues in motor neuron disease. J Neurol Neurosurg Psych 49(2):211–215
Yanagihara R, Garruto RM, Gajdusek DC, Tomita A, Uchikawa T, Konagaya Y, Chen KM, Sobue I, Plato CC, Gibbs CJ (1984) Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia. Ann Neurol 15(1):42–48
Garruto RM, Swyt C, Fiori CE, Yanagihara R, Gajdusek DC (1985) Intraneuronal deposition of calcium and aluminium in amyotropic lateral sclerosis of Guam. Lancet 2(8468):1353
Kjellin KG (1967) The CSF iron in patients with neurological diseases. Acta Neurol Scand 43(3):299–313
Chen KM (1995) Disappearance of ALS from Guam: implications for exogenous causes. Rinsho Shinkeigaku 35(12):1549–1553
Adamek D, Tomik B, Pichór A, Kałuża J, Szczudlik A (2002) Heterogeneity of neuropathological changes in ALS. The review of own autopsy material. Folia Neuropathologica 40:119–124
Acknowledgements
The authors are grateful to the Ministry of Education and Science, State Committee for Scientific Research grant 112/E-356/SPB/DESY/P-05/DWM728/2003–2005 and IHP-Contract HPRI-CT-1999-00040/2001-00140 of the European Commission. Thanks are also due to The European Community-Research Infrastructure Action under FP6 “Structuring the European Research Area” Programme (through the Integrated Infrastructure Initiative “Integrating Activity on Synchrotron and Free Electron Laser Science”) and Experimental grants: HASYLAB II-02–092 and ESRF LS 2111.
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Tomik, B., Chwiej, J., Szczerbowska-Boruchowska, M. et al. Implementation of X-ray Fluorescence Microscopy for Investigation of Elemental Abnormalities in Amyotrophic Lateral Sclerosis. Neurochem Res 31, 321–331 (2006). https://doi.org/10.1007/s11064-005-9030-6
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DOI: https://doi.org/10.1007/s11064-005-9030-6