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The spatial and temporal relationship between oxidative stress and neuronal degeneration in 3-nitropropionic acid model

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DOI: 10.4236/wjns.2012.24036    4,316 Downloads   7,067 Views   Citations


The current study investigates the role of oxidative stress and calcium homeostasis in the development of selective striatal lesions in metabolic impairment model caused by 3-nitropropionic acid (3NP). In this report, we examined the distribution of oxidative stress markers and the production of mitochondrial reactive oxygen species in the presence of 3NP in male Sprague-Dawley rats. Protein oxidation was assessed using 3-nitrotyrosine immunoreactivity, while DNA oxidative damage was evaluated by poly (ADP-ribose) polymerase-1 activity. The Reactive Oxygen Species (ROS) production was determined in isolated mitochondrial from striatum and cerebellum of two age groups following 3NP and variable calcium concentration. The results demonstrate that increased 3-nitro-tyrosine level is the most robust in the striatum and the least evident in the cerebellum following 4 days of 3NP treatment. No significant change in the levels of poly ADP-ribosylated proteins was observed, likely due to a rapid PARP-1 cleavage as detected by the appearance of 50 kDa necrotic fragment. In mitochondrial isolates, there was no immediate increase in mitochondrial ROS following 3NP in either striatum or cerebellum; however, calcium addition resulted in a concentration dependent increase in reactive oxygen species in striatal mitochondria of the older animals. These results suggest that in aging, mitochondria become more susceptible to the generation of ROS in conditions that cause a concurrent compromised in mitochondrial calcium concentration. This finding implicates mitochondria dysfunction as a key cellular target in pathological states that are associated with metabolic impairment. The results also reinforce the notion that mitochondrial function in the striatum and cerebellum respond differently to the aging process, which may explain the variable regional vulnerability in 3NP model.

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The authors declare no conflicts of interest.

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Delorme, T. , Najafi, M. and Nasr, P. (2012) The spatial and temporal relationship between oxidative stress and neuronal degeneration in 3-nitropropionic acid model. World Journal of Neuroscience, 2, 234-247. doi: 10.4236/wjns.2012.24036.


[1] James, L.F., et al. (1980) Field and experimental studies in cattle and sheep poisoned by nitro-bearing Astragalus or their toxins. American Journal of Veterinary Research, 41, 377-382.
[2] Hu, W.J. (1986) Isolation and structure determination of arthrinium toxin causing sugarcane poisoning. Nitropropionic Acid, 20, 321-323.
[3] Alston, T.A., Mela, L. and Bright, H.J. (1977) 3-nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proceedings of the National Academy of Sciences of the United States, 74, 3767-3771. doi:10.1073/pnas.74.9.3767
[4] Ludolph, A.C., et al. (1991) 3-nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Canadian Journal of Neurological Sciences, 18, 492-498.
[5] Borlongan, C.V., et al. (1997) Hyperactivity and hypo-activity in a rat model of Huntington’s disease: The systemic 3-nitropropionic acid model. Brain Research Protocols, 1, 253-257. doi:10.1016/S1385-299X(96)00037-2
[6] Borlongan, C.V., Koutouzis, T.K. and Sanberg, P.R. (1997) 3-Nitropropionic acid animal model and Huntington’s disease. Neuroscience & Biobehavioral Reviews, 21, 289-293. doi:10.1016/S0149-7634(96)00027-9
[7] Beal, M.F. (1994) Neurochemistry and toxin models in Huntington’s disease. Current Opinion in Neurology, 7, 542-547. doi:10.1097/00019052-199412000-00012
[8] Palfi, S., et al. (1996) Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington’s disease. The Journal of Neuroscience, 16, 3019-3025.
[9] He, F., et al. (1990) Mycotoxin-induced encephalopathy and dystonia in children. Taylor and Francis, London.
[10] He, F., et al. (1995) Delayed dystonia with striatal CT lucencies induced by a mycotoxin (3-nitropropionic acid). Neurology, 45, 2178-2183. doi:10.1212/WNL.45.12.2178
[11] Ming, L. (1995) Moldy sugarcane poisoning—A case report with a brief review. Journal of Toxicology—Clinical Toxicology, 33, 363-367. doi:10.3109/15563659509028924
[12] Borlongan, C.V., et al. (1995) Systemic 3-nitropropionic acid: Behavioral deficits and striatal damage in adult rats. Brain Research Bulletin, 36, 549-556. doi:10.1016/0361-9230(94)00242-S
[13] Borlongan, C.V., et al. (1995) Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motoric symptoms of Huntington’s. Brain Research, 697, 254-257. doi:10.1016/0006-8993(95)00901-2
[14] Nasr, P., Carbery, T. and Geddes, J.W. (2009) N-methyl-D-aspartate receptor antagonists have variable affect in 3-nitropropionic acid toxicity. Neurochemical Research, 34, 490-498. doi:10.1007/s11064-008-9809-3
[15] Butler, A.K., Uryu, K. and Chesselet, M.F. (1998) A role for N-methyl-D-aspartate receptors in the regulation of synaptogenesis and expression of the polysialylated form of the neural cell adhesion molecule in the developing striatum. Developmental Neuroscience, 20, 253-262. doi:10.1159/000017319
[16] Parent, A. and Hazrati, L.N. (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Research Reviews, 20, 91-127. doi:10.1016/0165-0173(94)00007-C
[17] Parent, A. and Hazrati, L.N. (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Research Reviews, 20, 128-154. doi:10.1016/0165-0173(94)00008-D
[18] Yung, K.K., et al. (1995) Immunocytochemical localiza- tion of D1 and D2 dopamine receptors in the basal ganglia of the rat: Light and electron microscopy. Neuroscience, 65, 709-730. doi:10.1016/0306-4522(94)00536-E
[19] Beal, M.F., et al. (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. The Journal of Neuroscience, 13, 4181-4192.
[20] Brouillet, E., et al. (1993) Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. Journal of Neurochemistry, 60, 356-359. doi:10.1111/j.1471-4159.1993.tb05859.x
[21] Bossi, S.R., Simpson, J.R. and Isacson, O. (1993) Age dependence of striatal neuronal death caused by mitochondrial dysfunction. Neuroreport, 4, 73-76. doi:10.1097/00001756-199301000-00019
[22] Pang, Z., Umberger, G.H. and Geddes, J.W. (1996) Neuronal loss and cytoskeletal disruption following intrahippocampal administration of the metabolic inhibitor malonate: Lack of protection by MK-801. Journal of Neuro- chemistry, 66, 474-484. doi:10.1046/j.1471-4159.1996.66020474.x
[23] Brouillet, E., et al. (1998) Partial inhibition of brain succinate dehydrogenase by 3-nitropropionic acid is sufficient to initiate striatal degeneration in rat. Journal of Neurochemistry, 70, 794-805. doi:10.1046/j.1471-4159.1998.70020794.x
[24] Novelli, A., et al. (1988) Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Research, 451, 205-212. doi:10.1016/0006-8993(88)90765-2
[25] Hamilton, B.F. and Gould, D.H. (1987) Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: A type of hypoxic (energy deficient) brain damage. Acta Neuropathologica (Berlin), 72, 286-297. doi:10.1007/BF00691103
[26] Binienda, Z., et al. (1998) Effect of acute exposure to 3-nitropropionic acid on activities of endogenous anti-oxidants in the rat brain. Neuroscience Letters, 251, 173-176. doi:10.1016/S0304-3940(98)00539-4
[27] Kim, G.W., et al. (2000) Excitotoxicity is required for induction of oxidative stress and apoptosis in mouse striatum by the mitochondrial toxin, 3-nitropropionic acid. Journal of Cerebral Blood Flow & Metabolism, 20, 119-129. doi:10.1097/00004647-200001000-00016
[28] Zeevalk, G.D., L.P. Bernard, and W.J. Nicklas, Oxidative stress during energy impairment in mesencephalic cultures is not a downstream consequence of a secondary excitotoxicity. Neuroscience, 96, 309-316. doi:10.1016/S0306-4522(99)00567-9
[29] Pang, Z. and Geddes, J.W. (1997) Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: Acute excitotoxic necrosis and delayed apoptosis. The Journal of Neuroscience, 17, 3064-3073.
[30] Brenman, J.E. and Bredt, D.S. (1997) Synaptic signaling by nitric oxide. Current Opinion in Neurobiology, 7, 374- 378. doi:10.1016/S0959-4388(97)80065-7
[31] Christopherson, K.S., et al. (1999) PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. The Journal of Biological Chemistry, 274, 27467-27473. doi:10.1074/jbc.274.39.27467
[32] Sattler, R., et al. (1999) Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science, 284, 1845-1848. doi:10.1126/science.284.5421.1845
[33] Moncada, S. and Palmer, R.M. (1991) Biosynthesis and actions of nitric oxide. Seminars in Perinatology, 15, 16-19.
[34] Knowles, R.G. and Moncada, S. (1994) Nitric oxide synthases in mammals. Biochemical Journal, 298, 249-258.
[35] Darley-Usmar, V., Wiseman, H. and Halliwell, B. (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Letters, 369, 131-135. doi:10.1016/0014-5793(95)00764-Z
[36] Zweier, J.L., et al. (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nature Medicine, 1, 804-809. doi:10.1038/nm0895-804
[37] Farinati, F., et al. (1996) Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection. Journal of Clinical Gastroenterology, 22, 275-281. doi:10.1097/00004836-199606000-00007
[38] Tamir, S. and Tannenbaum, S.R. (1996) The role of nitric oxide (NO.) in the carcinogenic process. Biochimica et Biophysica Acta, 1288, F31-F36.
[39] Beckman, J.S. and Koppenol, W.H. (1996) Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. American Journal of Physiology, 271, C1424-C1437.
[40] Pannala, A.S., et al. (1998) Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates: Nitration or electron donation. Free Radical Biology & Medicine, 24, 594-606. doi:10.1016/S0891-5849(97)00321-3
[41] Beckman, J.S. (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chemical Research in Toxicology, 9, 836-844. doi:10.1021/tx9501445
[42] Schulz, J.B., Matthews, R.T. and Beal, M.F. (1995) Role of nitric oxide in neurodegenerative diseases. Current Opinion in Neurology, 8, 480-486. doi:10.1097/00019052-199512000-00016
[43] Ischiropoulos, H. (1998) Biological tyrosine nitration: A pathophysiological function of nitric oxide and reactive oxygen species. Archives of Biochemistry and Biophysics, 356, 1-11. doi:10.1006/abbi.1998.0755
[44] Calabrese, V., Bates, T.E. and Stella, A.M. (2000) NO-synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: The role of oxidant/antioxidant balance. Neurochemical Research, 25, 1315-1341. doi:10.1023/A:1007604414773
[45] Calabrese, V., et al. (2002) Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. Journal of Neuroscience Research, 70, 580-587. doi:10.1002/jnr.10408
[46] Ha, H.C. and Snyder, S.H. (2000) Poly (ADP-ribose) polymerase-1 in the nervous system. Neurobiology of Disease, 7, 225-39. doi:10.1006/nbdi.2000.0324
[47] Reynolds, I.J. and Hastings, T.G. (1995) Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation. The Journal of Neuroscience, 15, 3318-3327.
[48] Dugan, L.L., et al. (1995) Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. The Journal of Neuroscience, 15, 6377-6388.
[49] Cadenas, E. and Boveris, A. (1980) Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria. Biochemical Journal, 188, 31-37.
[50] Sousa, S.C., et al. (2003) Ca2+-induced oxidative stress in brain mitochondria treated with the respiratory chain inhibitor rotenone. FEBS Letters, 543, 179-183. doi:10.1016/S0014-5793(03)00421-6
[51] Votyakova, T.V. and Reynolds, I.J. (2005) Ca2+-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I. The Journal of Neuroscience, 93, 526-537. doi:10.1111/j.1471-4159.2005.03042.x
[52] Peng, T.I. and Jou, M.J. (2010) Oxidative stress caused by mitochondrial calcium overload. Annals of the New York Academy of Sciences, 1201, 183-188. doi:10.1111/j.1749-6632.2010.05634.x
[53] Jacquard, C., et al. (2006) Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation. The FASEB Journal, 20, 1021-1023. doi:10.1096/fj.05-5085fje
[54] Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685. doi:10.1038/227680a0
[55] Sullivan, P.G., Thompson, M.B., and Scheff, S.W. (1999) CyclosporinA attenuates acute mitochondrial dysfunction following traumatic brain injury. Experimental Neurology, 160, 226-234. doi:10.1006/exnr.1999.7197
[56] Sullivan, P.G., Geiger, J.D., Mattson, M.P., and Scheff, S.W. (2000) Dietary supplement creatine protects against traumatic brain injury. Annals of Neurology, 48, 723-729. doi:10.1002/1531-8249(200011)48:5<723::AID-ANA5>3.0.CO;2-W
[57] Koutouzis, T.K., et al. (1994) Systemic 3-nitropropionic acid: Long-term effects on locomotor behavior. Brain Research, 646, 242-246. doi:10.1016/0006-8993(94)90085-X
[58] Koutouzis, T.K., et al., Intrastriatal 3-nitropropionic acid: a behavioral assessment. Neuroreport, 1994. 5(17): p. 2241-5. doi:10.1097/00001756-199411000-00009
[59] Borlongan, C.V., et al. (1995) Systemic 3-nitropropionic acid: Behavioral deficits and striatal damage in adult rats. Brain Research Bulletin, 36, 549-556. doi:10.1016/0361-9230(94)00242-S
[60] Gobeil, S., et al. (2001) Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): Implication of lysosomal proteases. Cell Death Differ, 8, 588- 594. doi:10.1038/sj.cdd.4400851
[61] Ha, H.C. and Snyder, S.H. (1999) Poly (ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proceedings of the National Academy of Sciences, 96, 13978-13982. doi:10.1073/pnas.96.24.13978
[62] Shah, G.M., Shah, R.G. and Poirier, G.G. (1996) Different cleavage pattern for poly (ADP-ribose) polymerase during necrosis and apoptosis in HL-60 cells. Biochemical and Biophysical Research Communications, 229, 838- 844. doi:10.1006/bbrc.1996.1889
[63] Perez Velazquez, J.L., Frantseva, M.V. and Carlen, P.L. (1997) In vitro ischemia promotes glutamate-mediated free radical generation and intracellular calcium accumulation in hippocampal pyramidal neurons. The Journal of Neuroscience, 17, 9085-9094.
[64] Tunez, I., et al. (2010) 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington’s disease: Past, present and future. Molecules, 15, 878-916. doi:10.3390/molecules15020878
[65] Wu, C.L., et al. (2010) Neuroprotective mechanisms of brain-derived neurotrophic factor against 3-nitropropionic acid toxicity: Therapeutic implications for Huntington’s disease. Annals of the New York Academy of Sciences, 1201, 8-12. doi:10.1111/j.1749-6632.2010.05628.x
[66] Choi, D.W. (1992) Excitotoxic cell death. Journal of Neurobiology, 23, 1261-1276. doi:10.1002/neu.480230915
[67] Coyle, J.T., et al. (1981) Excitatory amino acid neurotoxins: Selectivity, specificity, and mechanisms of action. Based on an NRP one-day conference held June 30, 1980. Neurosciences Research Program Bulletin, 19, 1-427.
[68] Rhee, S.G., et al. (1991) Multiple forms of phosphoinositide-specific phospholipase C and different modes of activation. Biochemical Society Transactions, 19, 337-341.
[69] Rothman, S.M. and Olney, J.W. (1986) Glutamate and the pathophysiology of hypoxic--ischemic brain damage. Annals of Neurology, 19, 105-111. doi:10.1002/ana.410190202
[70] Beal, M.F. (1992) Mechanisms of excitotoxicity in neurologic diseases. FASEB Journal, 6, 3338-3344.
[71] Coyle, J.T. and Puttfarcken, P. (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262, 689-695. doi:10.1126/science.7901908
[72] DiFiglia, M. (1990) Excitotoxic injury of the neostriatum: A model for Huntington’s disease. Trends in Neurosciences, 13, 286-289. doi:10.1016/0166-2236(90)90111-M
[73] Westerberg, E., et al. (1987) Excitatory amino acid receptors and ischemic brain damage in the rat. Neuroscience Letters, 73, 119-124. doi:10.1016/0304-3940(87)90004-8
[74] Olney, J.W. (1971) Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. Journal of Neuropathology & Experimental Neurology, 30, 75-90. doi:10.1097/00005072-197101000-00008
[75] Zeevalk, G.D. and Nicklas, W.J. (1991) Mechanisms underlying initiation of excitotoxicity associated with metabolic inhibition. Journal of Pharmacology and Experimental Therapeutics, 257, 870-878.
[76] Albin, R.L. and Greenamyre, J.T. (1992) Alternative excitotoxic hypotheses. Neurology, 42, 733-738. doi:10.1212/WNL.42.4.733
[77] Beal, M.F. (1992) Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses. Annals of Neurology, 31, 119-30. doi:10.1002/ana.410310202
[78] Beal, M.F. (1992) Role of excitotoxicity in human neurological disease. Current Opinion in Neurobiology, 2, 657- 662. doi:10.1016/0959-4388(92)90035-J
[79] Liot, G., et al. (2009) Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ, 16, 899-909. doi:10.1038/cdd.2009.22
[80] Schulz, J.B., et al. (1996) Involvement of oxidative stress in 3-nitropropionic acid neurotoxicity. Neurochemistry International, 29, 167-171. doi:10.1016/0197-0186(95)00122-0
[81] Schulz, J.B., et al. (1997) The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases. Molecular and Cellular Biochemistry, 174, 193-197. doi:10.1023/A:1006852306789
[82] Sies, H. and Cadenas, E. (1985) Oxidative stress: Damage to intact cells and organs. Philosophical Transactions of the Royal Society B: Biological Sciences, 311, 617-631. doi:10.1098/rstb.1985.0168
[83] A.E., et al. (1997) The role of reactive oxygen species in mitochondrial permeability transition. Bioscience Reports, 17, 43-52. doi:10.1023/A:1027335217774
[84] Beal, M.F., et al. (1995) 3-Nitropropionic acid neurotoxicity is attenuated in copper/zinc superoxide dismutase transgenic mice. Journal of Neurochemistry, 65, 919- 922.
[85] Galpern, W.R., et al. (1996) NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Hunting- ton’s disease. Neuroreport, 7, 2639-2642.
[86] Schulz, J.B., et al. (1995) Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo. The Journal of Neuroscience, 15, 8419-8429.
[87] Browne, S.E., et al. (1997) Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia. Annals of Neurology, 41, 646-653. doi:10.1002/ana.410410514
[88] Good, P.F., et al. (1998) Protein nitration in Parkinson’s disease. Journal of Neuropathology & Experimental Neurology, 57, 338-342. doi:10.1097/00005072-199804000-00006
[89] Hensley, K., et al. (1998) Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. The Journal of Neuroscience, 18, 8126-8132.
[90] Hanafy, K.A., Krumenacker, J.S. and Murad, F. (2001) NO, nitrotyrosine, and cyclic GMP in signal transduction. Medical Science Monitor, 7, 801-819.
[91] Kong, S.K., et al. (1996) Peroxynitrite disables the tyro- sine phosphorylation regulatory mechanism: Lymphocyte-specific tyrosine kinase fails to phosphorylate nitrated cdc2(6-20)NH2 peptide. Proceedings of the National Academy of Sciences of United States, 93, 3377-3382. doi:10.1073/pnas.93.8.3377
[92] Stadtman, E.R. (2001) Protein oxidation in aging and age-related diseases. Annals of the New York Academy of Sciences, 928, 22-38.
[93] Huie, R.E. and Padmaja, S. (1993) The reaction of no with superoxide. Free Radical Research Communications, 18, 195-199. doi:10.3109/10715769309145868
[94] Esposito, L.A., et al. (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proceedings of the National Academy of Sciences of United States, 96, 4820-4825. doi:10.1073/pnas.96.9.4820
[95] Geddes, J.W. and Pang, Z. (2000) Mechanisms of 3-nitropropionic acid toxicity. mitochondrial inhibitors and neurodegenerative disorders. In: Sanberg, P.R., Nishino, H. and Borlongan, C.V., Eds., Humana Press, Totowa, 107-120. doi:10.1007/978-1-59259-692-8_7
[96] Kaufmann, S.H., et al. (1993) Specific proteolytic cleavage of poly (ADP-ribose) polymerase: An early marker of chemotherapy-induced apoptosis. Cancer Research, 53, 3976-3985.
[97] Lazebnik, Y.A., et al. (1994) Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature, 371, 346-347. doi:10.1038/371346a0
[98] Kerr, J.F. (2002) History of the events leading to the formulation of the apoptosis concept. Toxicology, 181-182, 471-474. doi:10.1016/S0300-483X(02)00457-2
[99] Hamilton, B.F. and Gould, D.H. (1987) Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: A type of hypoxic (energy deficient) brain. Acta Neuropathologica (Berlin), 72, 286-297. doi:10.1007/BF00691103
[100] Miller, P.J. and Zaborszky, L. (1997) 3-Nitropropionic acid neurotoxicity: Visualization by silver staining and implications for use as an animal model of Huntington’s disease. Experimental Neurology, 146, 212-229. doi:10.1006/exnr.1997.6522
[101] Brinkhurst, F.R. and Potts, Jr., J.T. (1979) Calcium and phosphate distribution, turnover, and metabolic actions. Endocrinology, 2, 551-585.
[102] Kass, G.E. and Orrenius, S. (1999) Calcium signaling and cytotoxicity. Environmental Health Perspectives, 107, 25- 35.
[103] Cheung, W.Y. (1982) Calmodulin: An overview. Federation Proceedings, 41, 2253-2257.
[104] Rizzuto, R., et al. (1994) Mitochondrial Ca2+ homeostasis in intact cells. The Journal of Cell Biology, 126, 1183-1194. doi:10.1083/jcb.126.5.1183
[105] Rutter, G.A., et al. (1996) Subcellular imaging of intramitochondrial Ca2+ with recombinant targeted aequorin: Significance for the regulation of pyruvate dehydrogenase activity. Proceedings of the National Academy of Sciences of United States, 93, 5489-5494. doi:10.1073/pnas.93.11.5489
[106] Bernardi, P. (1999) Mitochondrial transport of cations: Channels, exchangers, and permeability transition. Physiological Reviews, 79, 1127-1155.
[107] Nicholls, D.G. (2004) Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Current Molecular Medicine, 4, 149-177. doi:10.2174/1566524043479239
[108] Jou, M.J., et al. (2004) Mitochondrial reactive oxygen species generation and calcium increase induced by visible light in astrocytes. Annals of the New York Academy of Sciences, 1011, 45-56. doi:10.1196/annals.1293.005
[109] Jou, M.J., et al. (2010) Visualization of melatonin’s multiple mitochondrial levels of protection against mitochondrial Ca(2+)-mediated permeability transition and beyond in rat brain astrocytes. Journal of Pineal Research, 48, 20-38. doi:10.1111/j.1600-079X.2009.00721.x
[110] Peng, T.I., et al. (2005) Mitochondrion-targeted photo-sensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis. Annals of the New York Academy of Sciences, 1042, 419-428. doi:10.1196/annals.1338.035
[111] Peng, T.I. and Jou, M.J. (2004) Mitochondrial swelling and generation of reactive oxygen species induced by photoirradiation are heterogeneously distributed. Annals of the New York Academy of Sciences, 1011, 112-122. doi:10.1196/annals.1293.012
[112] Sato, T. and Tauchi, H. (1982) Age changes of mitochondria of rat kidney. Mechanisms of Ageing and Development, 20, 111-126. doi:10.1016/0047-6374(82)90063-X
[113] Mecocci, P., MacGarvey, U. and Beal, M.F. (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Annals of Neurology, 36, 747-751. doi:10.1002/ana.410360510
[114] Kim, G.W. and Chan, P.H. (2001) Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum. Neurobiology of Disease, 8, 114-126. doi:10.1006/nbdi.2000.0327
[115] Sohal, R.S. and Weindruch, R. (1996) Oxidative stress, caloric restriction, and aging. Science, 273, 59-63. doi:10.1126/science.273.5271.59
[116] Beal, M.F., et al. (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. The Journal of Neuroscience, 13, 4181-4192.
[117] Brouillet, E. and Hantraye, P. (1995) Effects of chronic MPTP and 3-nitropropionic acid in nonhuman primates. Current Opinion in Neurology, 8, 469-473. doi:10.1097/00019052-199512000-00014
[118] Nishino, H., et al. (1995) Chronically administered 3-nitropropionic acid induces striatal lesions attributed to dysfunction of the blood-brain barrier. Neuroscience Letters, 186, 161-164. doi:10.1016/0304-3940(95)11311-J
[119] Nishino, H., et al. (2000) The striatum is the most vulnerable region in the brain to mitochondrial energy compromise: a hypothesis to explain its specific vulnerability. Journal of Neurotrauma, 17, 251-260. doi:10.1089/neu.2000.17.251
[120] Brustovetsky, N. and Dubinsky, J.M. (2000) Dual responses of CNS mitochondria to elevated calcium. The Journal of Neuroscience, 20, 103-113.
[121] Brustovetsky, N., et al. (2003) Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. The Journal of Neuroscience, 23, 4858-4867.
[122] Basso, E., et al. (2005) Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. The Journal of Biological Chemistry, 280, 18558-18561. doi:10.1074/jbc.C500089200
[123] Wullner, U., et al. (1994) 3-Nitropropionic acid toxicity in the striatum. Journal of Neurochemistry, 63, 1772-1781. doi:10.1046/j.1471-4159.1994.63051772.x
[124] Fu, Y., et al. (1995) 3-Nitropropionic acid produces indirect excitotoxic damage to rat striatum. Neurotoxicology and Teratology, 17, 333-339. doi:10.1016/0892-0362(94)00076-P
[125] Shimano, Y., et al. (1995) Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus. Obesity Research, 3, S779-S784. doi:10.1002/j.1550-8528.1995.tb00499.x
[126] Reynolds, D.S., Carter, R.J. and Morton, A.J. (1998) Dopamine modulates the susceptibility of striatal neurons to 3-nitropropionic acid in the rat model of Huntington’s disease. The Journal of Neuroscience, 18, 10116-10127.
[127] Pandey, M., et al. (2009) Striatal dopamine level contributes to hydroxyl radical generation and subsequent neurodegeneration in the striatum in 3-nitropropionic acidinduced Huntington’s disease in rats. Neurochemistry International, 55, 431-437. doi:10.1016/j.neuint.2009.04.013
[128] Villaran, R.F., et al. (2008) Endogenous dopamine enhances the neurotoxicity of 3-nitropropionic acid in the striatum through the increase of mitochondrial respiratory inhibition and free radicals production. Neurotoxicology, 29, 244-258.
[129] Lindal, S. (2002) Mitochondria and neurodegenerative diseases, is there a link? The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis (ALS). Ultrastructural Pathology, 26, 1-2. doi:10.1080/01913120252934251
[130] Horton, T.M., et al. (1995) Marked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington’s disease patients. Neurology, 45, 1879-1883. doi:10.1212/WNL.45.10.1879
[131] Hu, T. and Desai, J.P. (2004) Soft-tissue material properties under large deformation: Strain rate effect. Proceedings of the 26th Annual International Conference of the IEEE EMBS, San Francisco, 1-5 September 2004, 2758- 2761.

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