Resistance to NMDA toxicity correlates with appearance of nuclear inclusions, behavioural deficits and changes in calcium homeostasis in mice transgenic for exon 1 of the huntington gene

European Journal of Neuroscience

Volumn 14, Issue 9, 2001, Pages 1492-1504

  Hansson, Oskar ^a   Guatteo, Ezia ^b   Mercuri, Nicola B ^b,c   Bernardi, Giorgio ^b,c   Li, Xiao Jiang ^d   Castilho, Roger F ^a,e   Brundin, Patrik ^a  

^a LUND UNIVERSITY   (Sweden)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c UNIVERSITY OF ROME TOR VERGATA   (Italy)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF CAMPINAS   (Brazil)

Author keywords

Calcium; Cell death; Excitotoxicity; Huntington's disease; NMDA receptor; Striatum; Tolerance; Transgenic mouse

Indexed keywords

ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; CALCIUM ION; N METHYL DEXTRO ASPARTIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; BRAIN INJURY; BRAIN REGION; CALCIUM HOMEOSTASIS; CALCIUM TRANSPORT; CELL ASSAY; CELL NUCLEUS INCLUSION BODY; CONTROLLED STUDY; CORRELATION ANALYSIS; CYTOLYSIS; CYTOPLASM; DEREGULATION; EXON; FEMALE; HIPPOCAMPUS; HUNTINGTON CHOREA; MALE; MOTOR DYSFUNCTION; MOUSE; MOUSE STRAIN; NERVE CELL; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TIME; TRANSGENIC MOUSE;

AGING; ANIMALS; BEHAVIOR, ANIMAL; BRAIN; CALCIUM; CELL NUCLEUS; CELL SURVIVAL; DRUG RESISTANCE; EXCITATORY AMINO ACID AGONISTS; EXONS; FEMALE; HIPPOCAMPUS; HOMEOSTASIS; HUNTINGTON DISEASE; IMMUNOHISTOCHEMISTRY; INCLUSION BODIES; MALE; MICE; MICE, TRANSGENIC; NEOSTRIATUM; NERVE DEGENERATION; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; RECEPTORS, N-METHYL-D-ASPARTATE; TRINUCLEOTIDE REPEATS;

EID: 0035783462     PISSN: 0953816X     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.0953-816X.2001.01767.x     Document Type: Article

References (88)

1. Abe, H. & Nowak, T.S. Jr (1996) Gene expression and induced ischemic tolerance following brief insults. Acta Neurobiol. Exp., 56, 3-8.
2. Aronin, N., Chase, K., Young, C., Sapp, E., Schwarz, C., Matta, N., Kornreich, R., Landwehrmeyer, B., Bird, E., Beal, M.F., Vonsattel, J.P., Smith, T., Carraway, R., Boyce, F.M., Young, A.B., Penney, J.B. & DiFiglia, M. (1995) CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain. Neuron, 15, 1193-1201.
3. Bao, J., Sharp, A.H., Wagster, M.V., Becher, M., Schilling, G., Ross, C.A., Dawson, V.L. & Dawson, T.M. (1996) Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc. Natl Acad. Sci. USA, 93, 5037-5042.
4. Beal, M.F. (1992) Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann. Neurol., 31, 119-130.
5. Beal, M.F., Finn, S.F. & Brouillet, E. (1993) Evidence for the involvment of metabotropic glutamate receptors in striatal excitotoxic lesions in vivo. Neurodegeneration, 2, 81-91.
6. Beal, M.F., Kowall, N.W., Ellison, D.W., Mazurek, M.F., Swartz, K.J. & Martin, J.B. (1986) Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature, 321, 168-171.
7. Bernard, V., Somogyi, P. & Bolam, J.P. (1997) Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. J. Neurosci., 17, 819-833.
8. Berridge, M.J. (1998) Neuronal calcium signaling. Neuron, 21, 13-26.
9. Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V. & Greenamyre, J.T. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci., 3, 1301-1306.
10. 2+ concentrations. J. Exp. Biol., 201, 1141-1152.
11. Bindokas, V.P. & Miller, R.J. (1995) Excitotoxic degeneration is initiated at non-random sites in cultured rat cerebellar neurons. J. Neurosci., 15, 6999-7011.
12. Brocard, J.B., Tassetto, M. & Reynolds, I.J. (2001) Quantitative evaluation of mitochondrial calcium content in rat cortical neurones following a glutamate stimulus. J. Physiol. (Lond.), 531, 793-805.
13. Calabresi, P., Centonze, D., Pisani, A., Sancesario, G., Gubellini, P., Marfia, G.A. & Bernardi, G. (1998) Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: Implications for ischemia and Huntington's disease. Ann. Neurol., 43, 586-597.
14. Calabresi, P., Mercuri, N.B., Sancesario, G. & Bernardi, G. (1993) Electrophysiology of dopamine-denervated striatal neurons. Implications for Parkinson's disease. Brain, 116, 433-452.
15. Carter, R.J., Lione, L.A., Humby, T., Mangiarini, L., Mahal, A., Bates, G.P., Dunnett, S.B. & Morton, A.J. (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci., 19, 3248-3257.
16. Castilho, R.F., Hansson, O., Ward, M.W., Budd, S.L. & Nicholls, D.G. (1998) Mitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells. J. Neurosci., 18, 10277-10286.
17. Cepeda, C., Walsh, J.P., Peacock, W., Buchwald, N.A. & Levine, M.S. (1994) Neurophysiological, pharmacological and morphological properties of human caudate neurons recorded in vitro. Neuroscience, 59, 89-103.
18. Cha, J.H., Kosinski, C.M., Kerner, J.A., Alsdorf, S.A., Mangiarini, L., Davies, S.W., Penney, J.B., Bates, G.P. & Young, A.B. (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc. Natl Acad. Sci. USA, 95, 6480-6485.
19. Chen, J. & Simon, R. (1997) Ischemic tolerance in the brain. Neurology, 48, 306-311.
20. Chen, Q., Veenman, C.L. & Reiner, A. (1996) Cellular expression of ionotropic glutamate receptor subunits on specific striatal neuron types and its implication for striatal vulnerability in glutamate receptor-mediated excitotoxicity. Neuroscience, 73, 715-731.
21. Coggeshall, R.E. & Lekan, H.A. (1996) Methods for determining numbers of cells and synapses: A case for more uniform standards of review. J. Comp. Neurol., 364, 6-15.
22. Courtney, M.J., Enkvist, M.O. & Akerman, K.E. (1995) The calcium response to the excitotoxin kainate is amplified by subsequent reduction of extracellular sodium. Neuroscience, 68, 1051-1057.
23. Cummings, C.J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H.T., Beaudet, A.L. & Zoghbi, H.Y. (1999) Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron, 24, 879-892.
24. Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. & Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537-548.
25. Di Iorio, P., Battaglia, G., Ciccarelli, R., Ballerini, P., Giuliani, P., Poli, A., Nicoletti, F. & Caciagli, F. (1996) Interaction between A1 adenosine and class II metabotropic glutamate receptors in the regulation of purine and glutamate release from rat hippocampal slices. J. Neurochem., 67, 302-309.
26. DiFiglia, M. (1990) Excitotoxic injury of the neostriatum: A model for Huntington's disease. Trends Neurosci., 13, 286-289.
27. DiFiglia, M., Sapp, E., Chase, K.O., Davies, S.W., Bates, G.P., Vonsattel, J.P. & Aronin, N. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 277, 1990-1993.
28. Ferrante, R.J., Andreassen, O.A., Jenkins, B.G., Dedeoglu, A., Kuemmerle, S., Kubilus, J.K., Kaddurah-Daouk, R., Hersch, S.M. & Beal, M.F. (2000) Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci., 20, 4389-4397.
29. Goto, S., Hirano, A. & Rojas-Corona, R.R. (1989) An immunohistochemical investigation of the human neostriatum in Huntington's disease. Ann. Neurol., 25, 298-304.
30. Gotz, T., Kraushaar, U., Geiger, J., Lubke, J., Berger, T. & Jonas, P. (1997) Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons. J. Neurosci., 17, 204-215.
31. Grynkiewicz, G., Poenie, M. & Tsien, R.Y. (1985) A new generation of calcium indicators with greatly improved fluorescence properties. J. Biol. Chem., 260, 3440-3450.
32. Guatteo, E., Mercuri, N.B., Bernardi, G. & Knopfel, T. (1998) Intracellular sodium and calcium homeostasis during hypoxia in dopamine neurons of rat substantia nigra pars compacta. J. Neurophysiol., 80, 2237-2243.
33. Gusella, J.F. & MacDonald, M.E. (2000) Molecular genetics: Unmasking polyglutamine triggers in neurodegenerative disease. Nature Rev., 1, 109-115.
34. Gutekunst, C.A., Li, S.H., Yi, H., Mulroy, J.S., Kuemmerle, S., Jones, R., Rye, D., Ferrante, R.J., Hersch, S.M. & Li, X.J. (1999) Nuclear and neuropil aggregates in Huntington's disease: Relationship to neuropathology. J. Neurosci., 19, 2522-2534.
35. Hansson, O., Castilho, R.F., Kaminski Schierle, G.S., Karlsson, J., Nicotera, P., Leist, M. & Brundin, P. (2000) Additive effects of caspase inhibitor and lazaroid on the survival of transplanted rat and human embryonic dopamine neurons. Exp. Neurol., 164, 102-111.
36. Hansson, O., Castilho, R.F., Korhonen, L., Lindholm, D., Bates, G. & Brundin, P. (2001) Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's Disease is dependent on age and CAG repeat length. J. Neurochem., 78, 694-703.
37. Hansson, O., Petersen, A., Leist, M., Nicotera, P., Castilho, R.F. & Brundin, P. (1999) Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. Proc. Natl Acad. Sci. USA, 96, 8727-8732.
38. HDCRG (Huntington's Disease Collaborative Research Group) (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971-983.
39. Hickey, M.A. & Morton, A.J. (2000) Mice transgenic for the Huntington's disease mutation are resistant to chronic 3-nitropropionic acid-induced striatal toxicity. J. Neurochem., 75, 2163-2171.
40. Hodgson, J.G., Agopyan, N., Gutekunst, C.A., Leavitt, B.R., LePiane, F., Singaraja, R., Smith, D.J., Bissada, N., McCutcheon, K., Nasir, J., Jamot, L., Li, X.J., Stevens, M.E., Rosemond, E., Roder, J.C., Phillips, A.G., Rubin, E.M., Hersch, S.M. & Hayden, M.R. (1999) A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron, 23, 181-192.
41. 2+ changes in rat forebrain neurones. J. Physiol. (Lond.), 509, 103-116.
42. Iannicola, C., Moreno, S., Oliverio, S., Nardacci, R., Ciofi-Luzzatto, A. & Piacentini, M. (2000) Early alterations in gene expression and cell morphology in a mouse model of Huntington's disease. J. Neurochem., 75 , 830-839.
43. Ishida, T., Yarimizu, K., Gute, D.C. & Korthuis, R.J. (1997) Mechanisms of ischemic preconditioning. Shock, 8, 86-94.
44. +. J. Neurochem., 71, 112-124.
45. Jenkins, B.G., Klivenyi, P., Kustermann, E., Andreassen, O.A., Ferrante, R.J., Rosen, B.R. & Beal, M.F. (2000) Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice. J. Neurochem., 74, 2108-2119.
46. Jiang, Z.G. & North, R.A. (1991) Membrane properties and synaptic responses of rat striatal neurones in vitro. J. Physiol. (Lond.), 443, 533-553.
47. Jiao, Y., Sun, Z., Lee, T., Fusco, F.R., Kimble, T.D., Meade, C.A., Cuthbertson, S. & Reiner, A. (1999) A simple and sensitive antigen retrieval method for free-floating and slide-mounted tissue sections. J. Neurosci. Meth., 93, 149-162.
48. Kawai, K., Nakagomi, T., Kirino, T., Tamura, A. & Kawai, N. (1998) Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functionally protects CA1 neurons in the gerbil. J. Cereb. Blood Flow Metab., 18, 288-296.
49. Kiedrowski (1998) The difference between mechanims of kainate and glutamate excitotoxicity in vitro: Osmotic lesion versus mitochondrial depolarisation. Restor. Neurol. Neurosci, 12, 71-79.
50. Kim, M., Lee, H.S., LaForet, G., McIntyre, C., Martin, E.J., Chang, P., Kim, T.W., Williams, M., Reddy, P.H., Tagle, D., Boyce, F.M., Won, L., Heller, A., Aronin, N. & DiFiglia, M. (1999) Mutant huntingtin expression in clonal striatal cells: Dissociation of inclusion formation and neuronal survival by caspase inhibition. J. Neurosci., 19, 964-973.
51. Klement, I.A., Skinner, P.J., Kaytor, M.D., Yi, H., Hersch, S.M., Clark, H.B., Zoghbi, H.Y. & Orr, H.T. (1998) Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell, 95, 41-53.
52. Kuemmerle, S., Gutekunst, C.A., Klein, A.M., Li, X.J., Li, S.H., Beal, M.F., Hersch, S.M. & Ferrante, R.J. (1999) Huntington aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol., 46, 842-849.
53. Levine, S.M., Klapstein, G.J., Koppel, A., Gruen, E., Cepeda, C., Vargas, M.E., Jokel, E.S., Carpenter, E.M., Zanjani, H., Hurst, R.S., Efstratiadis, A., Zitlin, S. & Chesselet, M.-F. (1999) Enhanced sensitivity to N-Methyl-D-Aspartate receptor activation in transgenic and knockin mouse model of Huntington's disease. J. Neurosci. Res., 58, 515-532.
54. Li, X.J., Li, S.H., Sharp, A.H., Nucifora, F.C. Jr, Schilling, G., Lanahan, A., Worley, P., Snyder, S.H. & Ross, C.A. (1995) A huntingtin-associated protein enriched in brain with implications for pathology. Nature, 378, 398-402.
55. Lin, X., Antalffy, B., Kang, D., Orr, H.T. & Zoghbi, H.Y. (2000) Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1. Nature Neurosci., 3, 157-163.
56. Lione, L.A., Carter, R.J., Hunt, M.J., Bates, G.P., Morton, A.J. & Dunnett, S.B. (1999) Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J. Neurosci., 19, 10428-10437.
57. Luthi-Carter, R., Strand, A., Peters, N.L., Solano, S.M., Hollingsworth, Z.R., Menon, A.S., Frey, A.S., Spektor, B.S., Penney, E.B., Schilling, G., Ross, C.A., Borchelt, D.R., Tapscott, S.J., Young, A.B., Cha, J.H. & Olson, J.M. (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol. Genet., 9, 1259-1271.
58. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. & Bates, G.P. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493-506.
59. Meldrum, B.S. (1994) The role of glutamate in epilepsy and other CNS disorders. Neurology, 44, S14-S23.
60. Morton, A.J. & Leavens, W. (2000) Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res. Bull., 52, 51-59.
61. Murphy, K.P., Carter, R.J., Lione, L.A., Mangiarini, L., Mahal, A., Bates, G.P., Dunnett, S.B. & Morton, A.J. (2000) Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation. J. Neurosci., 20, 5115-5123.
62. Nakata, N., Kato, H., Liu, Y. & Kogure, K. (1992) Effects of pretreatment with sublethal ischemia on the extracellular glutamate concentrations during secondary ischemia in the gerbil hippocampus evaluated with intracerebral microdialysis. Neurosci. Lett., 138, 86-88.
63. NicNiocaill, B., Haraldsson, B., Hansson, O., O'Connor, W.T. & Brundin, P. (2001) Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice. Eur. J. Neurosci., 13, 206-210.
64. Ohta, S., Furuta, S., Matsubara, I., Kohno, K., Kumon, Y. & Sakaki, S. (1996) Calcium movement in ischemia-tolerant hippocampal CA1 neurons after transient forebrain ischemia in gerbils. J. Cereb. Blood Flow Metab., 16, 915-922.
65. Peng, T.I. & Greenamyre, J.T. (1998) Privileged access to mitochondria of calcium influx through N-methyl-D-aspartate receptors. Mol. Pharmacol., 53 , 974-980.
66. Perez-Severiano, F., Rios, C. & Segovia, J. (2000) Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington's disease. Brain Res., 862, 234-237.
67. Petersén, A., Hansson, O., Puschban, Z., Sapp, E., Romero, N., Castilho, R.F., Sulzer, D., Rice, M., DiFiglia, M., Przedborski, S. & Brundin, P., (2001) Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine. Eur. J. Neurosci., 14, 1425-1435.
68. Rego, A.C., Ward, M.W. & Nicholls, D.G. (2001) Mitochondria control ampa/kainate receptor-induced cytoplasmic calcium deregulation in rat cerebellar granule cells. J. Neurosci., 21, 1893-1901.
69. Reynolds, I.J. (1998) Intracellular calcium and magnesium: Critical determinants of excitotoxicity? Prog. Brain Res., 116, 225-243.
70. Sattler, R. & Tymianski, M. (2000) Molecular mechanisms of calcium-dependent excitotoxicity. J. Mol. Med., 78, 3-13.
71. Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55-66.
72. Schauwecker, P.E. & Steward, O. (1997) Genetic determinants of susceptibility to excitotoxic cell death: Implications for gene targeting approaches. Proc. Natl Acad. Sci. USA, 94, 4103-4108.
73. Scherzinger, E., Sittler, A., Schweiger, K., Heiser, V., Lurz, R., Hasenbank, R., Bates, G.P., Lehrach, H. & Wanker, E.E. (1999) Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology. Proc. Natl Acad. Sci. USA, 96 , 4604-4609.
74. Schmued, L.C., Albertson, C. & Slikker, W. Jr (1997) Fluoro-Jade: A novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res., 751, 37-46.
75. Schmued, L.C. & Hopkins, K.J. (2000) Fluoro-Jade: novel fluorochromes for detecting toxicant-induced neuronal degeneration. Toxicol. Pathol., 28, 91-99.
76. Stout, A.K., Raphael, H.M., Kanterewicz, B.I., Klann, E. & Reynolds, I.J. (1998) Glutamate-induced neuron death requires mitochondrial calcium uptake. Nature Neurosci., 1, 366-373.
77. Tabrizi, S.J., Workman, J., Hart, P.E., Mangiarini, L., Mahal, A., Bates, G., Cooper, J.M. & Schapira, A.H. (2000) Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann. Neurol., 47, 80-86.
78. Tallaksen-Greene, S.J. & Albin, R.L. (1996) Splice variants of glutamate receptor subunits 2 and 3 in striatal projection neurons. Neuroscience, 75, 1057-1064.
79. Tanaka, C., Nishino, N., Hashimoto, T., Kitamura, N., Yoshihara, C. & Saito, N. (1993) Second messenger systems in brains of patients with Parkinson's or Huntington's disease. Adv. Neurol., 60, 175-180.
80. Tomai, F., Crea, F., Chiariello, L. & Gioffre, P.A. (1999) Ischemic preconditioning in humans: Models, mediators, and clinical relevance. Circulation, 100, 559-563.
81. Trottier, Y., Devys, D., Imbert, G., Saudou, F., An, I., Lutz, Y., Weber, C., Agid, Y., Hirsch, E.C. & Mandel, J.L. (1995a) Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form. Nature Genet., 10, 104-110.
82. Trottier, Y., Lutz, Y., Stevanin, G., Imbert, G., Devys, D., Cancel, G., Saudou, F., Weber, C., David, G., Tora, L. et al. (1995b) Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature, 378, 403-406.
83. Turmaine, M., Raza, A., Mahal, A., Mangiarini, L., Bates, G.P. & Davies, S.W. (2000) Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc. Natl Acad. Sci. USA, 97, 8093-8097.
84. Vonsattel, J.P. & DiFiglia, M. (1998) Huntington disease. J. Neuropathol. Exp. Neurol., 57, 369-384.
85. Warsh, J.J., Politsky, J.M., Li, P.P., Kish, S.J. & Hornykiewicz, O. (1991) Reduced striatal [3H]inositol 1,4,5-trisphosphate binding in Huntington's disease. J. Neurochem., 56, 1417-1422.
86. West, M.J., Slomianka, L. & Gundersen, H.J. (1991) Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec., 231, 482-497.
87. Zeron, M.M., Hansson, O., Chen, N., Wellington, C.L., Leavitt, B.R., Brundin, P., Hayden, M.R., Raymond, L.A., Increased sensitivity to, N. & -methyl, D., (2001) Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron, in press.
88. Zuch, C.L., Nordstroem, V.K., Briedrick, L.A., Hoernig, G.R., Granholm, A.C. & Bickford, P.C. (2000) Time course of degenerative alterations in nigral dopaminergic neurons following a 6-hydroxydopamine lesion. J. Comp. Neurol., 427, 440-454.