Complexity and heterogeneity: What drives the ever-changing brain in Huntington's disease?

Annals of the New York Academy of Sciences

Volumn 1147, Issue , 2008, Pages 196-205

  Rosas, H Diana ^a   Salat, David H ^a   Lee, Stephanie Y ^a   Zaleta, Alexandra K ^a   Hevelone, Nathanael ^b   Hersch, Steven M ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Circuitry; Cortex; Huntington's disease; Neurodegeneration; Oxidative stress; Premanifest HD; Subcortical atrophy; White matter degeneration

Indexed keywords

BRAIN CORTEX; BRAIN REGION; CLINICAL FEATURE; CONFERENCE PAPER; CORPUS STRIATUM; DEGENERATIVE DISEASE; DISEASE COURSE; GENE MUTATION; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; NEOSTRIATUM; NEUROPATHOLOGY; OXIDATIVE STRESS; PATHOPHYSIOLOGY; WHITE MATTER;

EID: 57649198470     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1196/annals.1427.034     Document Type: Conference Paper

References (83)

1. Kremer, B. et al. 1994. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N. Engl. J. Med. 330 : 1401 1406.
2. Myers, R.H., M.E. MacDonald & J.F. Gusella. 1993. Discrepancy resolved. Nat. Genet. 5 : 215.
3. Anderson, K.E. et al. 2001. Cognitive correlates of obsessive and compulsive symptoms in Huntington's disease. Am. J. Psychiatry 158 : 799 801.
4. Rosenblatt, A. & I. Leroi. 2000. Neuropsychiatry of Huntington's disease and other basal ganglia disorders. Psychosomatics 41 : 24 30.
5. Hersch, S.M. 2003. Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation. Curr. Opin. Neurol. 16 : 501 506.
6. Group, H. S. D.C.R. 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 72 : 971 983.
7. Quarrell, O.W. et al. 2007. Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study. J. Med. Genet. 44 : e68.
8. Wheeler, V.C. et al. 2007. Factors associated with HD CAG repeat instability in Huntington disease. J. Med. Genet. 44 : 695 701.
9. Myers, R.H. 2004. Huntington's disease genetics. NeuroRx. 1 : 255 262.
10. Andresen, J.M. et al. 2007. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset. Ann. Hum. Genet. 71 : 295 301.
11. Andrew, S.E. et al. 1993. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat. Genet. 4 : 398 403.
12. Gutekunst, C.A. et al. 1999. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 19 : 2522 2534.
13. Vonsattel, J.P. et al. 1985. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 44 : 559 577.
14. Ferrante, R.J., N.W. Kowall & E.P. Richardson, Jr. 1991. Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J. Neurosci. 11 : 3877 3887.
15. Sotrel, A. et al. 1993. Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington's disease: a quantitative Golgi study. Neurology 43 : 2088 2096.
16. Milnerwood, A.J. & L.A. Raymond. 2007. Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load. J. Physiol. 585 : 817 831.
17. Murphy, K.P. et al. 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.
18. Laforet, G.A. et al. 2001. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J. Neurosci. 21 : 9112 9123.
19. Cepeda, C. et al. 2007. The corticostriatal pathway in Huntington's disease. Prog. Neurobiol. 81 : 253 271.
20. DiFiglia, M. et al. 1995. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14 : 1075 1081.
21. Persichetti, F. et al. 1994. Huntington's disease CAG trinucleotide repeats in pathologically confirmed post-mortem brains. Neurobiol. Dis. 1 : 159 166.
22. Zuccato, C. et al. 2001. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 293 : 493 48.
23. Cattaneo, E. et al. 2001. Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci. 24 : 182 188.
24. Goldberg, Y.P. et al. 1996. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat. Genet. 13 : 442 449.
25. Wellington, C.L. et al. 1998. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem. 273 : 9158 9167.
26. Wellington, C.L. & M.R. Hayden. 1997. Of molecular interactions, mice and mechanisms: new insights into Huntington's disease. Curr. Opin. Neurol. 10 : 291 298.
27. Davies, S.W. et al. 1997. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90 : 537 548.
28. Paulson, H.L. 1999. Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold. Am. J. Hum. Genet. 64 : 339 345.
29. Jana, N.R. et al. 2000. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 9 : 2009 2018.
30. Chai, Y. et al. 1999. Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum. Mol. Genet. 8 : 673 682.
31. Kazantsev, A. et al. 1999. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl. Acad. Sci. USA 96 : 11404 11409.
32. Steffan, J.S. et al. 2000. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 97 : 6763 6768.
33. Steffan, J.S. et al. 2001. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413 : 739 743.
34. Holbert, S. et al. 2001. The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl. Acad. Sci. USA 98 : 1811 1816.
35. Nucifora, F.C., Jr. et al. 2001. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291 : 2423 2428.
36. Gomez-Tortosa, E. et al. 2001. Quantitative neuropathological changes in presymptomatic Huntington's disease. Ann. Neurol. 49 : 29 34.
37. Perutz, M.F. & A.H. Windle. 2001. Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Nature 412 : 143 144.
38. Hodges, A. et al. 2006. Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet. 15 : 965 977.
39. Brochier, C. et al. 2008. Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in man and affected in disease models. Physiol. Genomics. 33 : 170 179.
40. Gu, M. et al. 1996. Mitochondrial defect in Huntington's disease caudate nucleus. Ann. Neurol. 39 : 385 389.
41. Bowling, A.C. & M.F. Beal. 1995. Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci. 56 : 1151 1171.
42. Browne, S.E. & M.F. Beal. 2006. Oxidative damage in Huntington's disease pathogenesis. Antioxid. Redox. Signal. 8 : 2061 2073.
43. Tabrizi, S.J. et al. 1999. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann. Neurol. 45 : 25 32.
44. Parker, W.D., Jr. et al. 1990. Evidence for a defect in NADH: ubiquinone oxidoreductase (complex I) in Huntington's disease. Neurology 40 : 1231 1234.
45. Weydt, P. et al. 2006. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab. 4 : 349 362.
46. Koroshetz, W.J. et al. 1997. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann. Neurol. 41 : 160 165.
47. Jenkins, B.G. et al. 2005. Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease. J. Neurochem. 95 : 553 562.
48. Fernandes, H.B. et al. 2007. Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease. J. Neurosci. 27 : 13614 13623.
49. Lim, D. et al. 2008. Calcium homeostasis and mitochondrial dysfunction in striatal neurons of huntington disease. J. Biol. Chem. 283 : 5780 5789.
50. Oliveira, J.M. et al. 2007. Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J. Neurochem. 101 : 241 249.
51. Grunewald, T. & M.F. Beal. 1999. Bioenergetics in Huntington's disease. Ann. N. Y. Acad. Sci. 893 : 203 213.
52. Brouillet, E. et al. 1995. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc. Natl. Acad. Sci. USA 92 : 7105 7109.
53. Beal, M.F. et al. 1992. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex. J. Neurol. Sci. 108 : 80 87.
54. Beal, M.F. 1992. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann. Neurol. 31 : 119 130.
55. Chen, C.M. et al. 2007. Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington's disease patients. Biochem. Biophys. Res. Commun. 359 : 335 340.
56. Hersch, S.M. et al. 2006. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology 66 : 250 252.
57. Polidori, M.C. et al. 1999. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex. Neurosci. Lett. 272 : 53 56.
58. Rong, J. et al. 2006. Regulation of intracellular trafficking of huntingtin-associated protein-1 is critical for TrkA protein levels and neurite outgrowth. J. Neurosci. 26 : 6019 6030.
59. Orr, A.L. et al. 2008. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J. Neurosci. 28 : 2783 2792.
60. Trushina, E. et al. 2004. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell Biol. 24 : 8195 8209.
61. McGill, J.K. & M.F. Beal. 2006. PGC-1alpha, a new therapeutic target in Huntington's disease? Cell 127 : 465 468.
62. Fischl, B. et al. 2002. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33 : 341 355.
63. Fischl, B., A. Liu & A.M. Dale. 2001. Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex. IEEE Trans. Med. Imaging 20 : 70 80.
64. Aylward, E.H. et al. 1994. Reduced basal ganglia volume associated with the gene for Huntington's disease in asymptomatic at-risk persons. Neurology 44 : 823 828.
65. Aylward, E.H. et al. 2004. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 63 : 66 72.
66. Georgiou-Karistianis, N. et al. 2007. Increased cortical recruitment in Huntington's disease using a Simon task. Neuropsychologia 45 : 1791 1800.
67. Saft, C. et al. 2008. fMRI reveals altered auditory processing in manifest and premanifest Huntington's disease. Neuropsychologia 46 : 1279 1289.
68. Wolf, R.C. et al. 2007. Dorsolateral prefrontal cortex dysfunction in presymptomatic Huntington's disease: evidence from event-related fMRI. Brain 130 : 2845 2857.
69. Buckner, R.L. & J.L. Vincent. 2007. Unrest at rest: default activity and spontaneous network correlations. NeuroImage 37 : 1091 1096 discussion 1097-9.
70. Rosas, H.D. et al. 2005. Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 65 : 745 747.
71. Langbehn, D.R. et al. 2004. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clin. Genet. 65 : 267 277.
72. Rosas, H.D. et al. 2008. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity. Brain 131 : 1057 1068.
73. Sapp, E. et al. 1997. Huntingtin localization in brains of normal and Huntington's disease patients. Ann. Neurol. 42 : 604 612.
74. Rosas, H.D. et al. 2006. Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures. Mov. Disord. 21 : 1317 1325.
75. Fennema-Notestine, C. et al. 2004. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease. Neurology 63 : 989 995.
76. de la Monte, S.M., J.P. Vonsattel & E.P. Richardson, Jr. 1988. Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington's disease. J. Neuropathol. Exp. Neurol. 47 : 516 525.
77. Group, H.S. 1996. Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov. Disord. 11 : 136 142.
78. Lawrence, A.D. et al. 2000. Visual object and visuospatial cognition in Huntington's disease: implications for information processing in corticostriatal circuits. Brain 123 (Pt 7 1349 1364.
79. Kipps, C.M. et al. 2005. Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study. J. Neurol. Neurosurg. Psychiatry 76 : 650 655.
80. Kassubek, J. et al. 2004. Global cerebral atrophy in early stages of Huntington's disease: quantitative MRI study. Neuroreport 15 : 363 365.
81. Peinemann, A. et al. 2005. Executive dysfunction in early stages of Huntington's disease is associated with striatal and insular atrophy: a neuropsychological and voxel-based morphometric study. J. Neurol. Sci. 239 : 11 19.
82. Kipps, C.M. et al. 2007. Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington's disease. J. Cogn. Neurosci. 19 : 1206 1217.
83. Berardelli, A. et al. 2001. Pathophysiology of bradykinesia in Parkinson's disease. Brain 124 : 2131 2146.