Skip to main content
SpringerLink
Log in
Book cover

Folding for the Synapse pp 233–255Cite as

Synaptic Dysfunction in Huntington’s Disease

  • Chapter
  • First Online:

  • 643 Accesses

Abstract

Huntington’s disease (HD) is a progressive, inherited, neurodegenerative disorder characterised by movement abnormalities, cognitive impairments and emotional disturbance (Bates et al. 2002). The genetic mutation for HD is an unstable CAG repeat expansion in the HD gene (Huntington’s Disease Collaborative Research Group 1993). The HD gene codes for a protein named huntingtin, and the CAG repeat is translated to an expanded polyglutamine repeat in the disease protein. However, even though the genetic mutation was identified more than 15 years ago, it is still not known how it causes HD. Until recently, the prevailing hypothesis was that the clinical manifestations of HD were due to selective neuronal degeneration in the striatum and cortex. Nevertheless, there is a growing body of work supporting the idea that some of the earliest changes apparent in HD, in particular changes in personality, mood and cognitive performance, may arise as a consequence of ­synaptic dysfunction. Here, we discuss the idea that synaptic dysfunction (rather than frank cell loss) may underlie early symptoms in HD.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   229.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Andre VM, Cepeda C, Venegas A et al (2006) Altered cortical glutamate receptor function in the R6/2 model of Huntington’s disease. J Neurophysiol 95:2108–2119

    Article  PubMed  CAS  Google Scholar 

  • Andrews TC, Weeks RA, Turjanski N et al (1999) Huntington’s disease progression. PET and clinical observations. Brain 122:2353–2363

    Article  PubMed  Google Scholar 

  • Antonini A, Leenders KL, Spiegel R et al (1996) Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington’s disease. Brain 119:2085–2095

    Article  PubMed  Google Scholar 

  • Barr AM, Hofmann CE, Phillips AG et al (2005) Prenatal ethanol exposure in rats decreases levels of complexin proteins in the frontal cortex. Alcohol Clin Exp Res 29:1915–1920

    Article  PubMed  CAS  Google Scholar 

  • Basso M, Giraudo S, Corpillo D et al (2004) Proteome analysis of human substantia nigra in Parkinson’s disease. Proteomics 4:3943–3952

    Article  PubMed  CAS  Google Scholar 

  • Bates G, Harper PS, Jones L (2002) Huntington’s disease (3rd Edn) Oxford University Press, Oxford

    Google Scholar 

  • Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292:1552–1555

    Article  PubMed  CAS  Google Scholar 

  • Bird ED, Iversen LL (1974) Huntington’s chorea: measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain 97:457–472

    Article  PubMed  CAS  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  • Block-Galarza J, Chase KO, Sapp E et al (1997) Fast transport and retrograde movement of huntingtin and HAP 1 in axons. Neuroreport 8:2247–2251

    Article  PubMed  CAS  Google Scholar 

  • Bowman AB, Yoo SY, Dantuma NP et al (2005) Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum Mol Genet 14:679–691

    Article  PubMed  CAS  Google Scholar 

  • Brandt J, Butters N (1986) The neuropsychology of Huntington’s disease. Trends Neurosci 9:118–120

    Article  Google Scholar 

  • Brose N (2008) Altered complexin expression in psychiatric and neurological disorders: cause or consequence? Mol Cells 25:7–19

    PubMed  CAS  Google Scholar 

  • Butterworth MB, Frizzell RA, Johnson JP et al (2005) PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin. Am J Physiol Renal Physiol 289:F969–F977

    Article  PubMed  CAS  Google Scholar 

  • Cai H, Reim K, Varoqueaux F et al (2008) Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming. Proc Natl Acad Sci U S A 105:19538–19543

    Article  PubMed  CAS  Google Scholar 

  • Carter RJ, Lione, LA, Humby T et al (1999) Characterisation of progressive motor deficits in mice transgenic for the Huntington’s disease mutation. J Neurosci 19:3248–3257

    PubMed  CAS  Google Scholar 

  • Castro ME, Pascual J, Romon T et al (1998) 5-HT1B receptor binding in degenerative movement disorders. Brain Res 790:323–328

    Article  PubMed  CAS  Google Scholar 

  • Cattaneo E, Zuccato C, Tartari M (2005) Normal huntingtin function: an alternative approach to Huntington’s disease. Nat Rev Neurosci 6:919–930

    Article  PubMed  CAS  Google Scholar 

  • Cepeda C, Ariano MA, Calvert CR et al (2001) NMDA receptor function in mouse models of Huntington disease. J Neurosci Res 66:525–539

    Article  PubMed  CAS  Google Scholar 

  • Cepeda C, Hurst RS, Calvert CR et al (2003) Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington’s disease. J Neurosci 23:961–969

    PubMed  CAS  Google Scholar 

  • Cepeda C, Wu N, Andre VM et al (2007) The corticostriatal pathway in Huntington’s disease. Prog Neurobiol 81:253–271

    Article  PubMed  CAS  Google Scholar 

  • Cha JH, Kosinski CM, Kerner JA et al (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485

    Article  PubMed  CAS  Google Scholar 

  • Cha JH, Frey AS, Alsdorf SA et al (1999) Altered neurotransmitter receptor expression in transgenic mouse models of Huntington’s disease. Philos Trans R Soc Lond A 354:981–989

    Article  CAS  Google Scholar 

  • Chen X, Tomchick DR, Kovrigin E et al (2002) Three-dimensional structure of the complexin/SNARE complex. Neuron 33:397–409

    Article  PubMed  CAS  Google Scholar 

  • Ciechanover A, Brundin P (2003) The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron 40:427–446

    Article  PubMed  CAS  Google Scholar 

  • Cummings DM, Milnerwood AJ, Dallérac GM et al (2007) Abnormal cortical synaptic plasticity in a mouse model of Huntington’s disease. Brain Res Bull 72:103–107

    Article  PubMed  CAS  Google Scholar 

  • Davies SW, Turmaine M, Cozens BA et al (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537–548

    Article  PubMed  CAS  Google Scholar 

  • Davies S, Ramsden DB (2001) Huntington’s disease. Mol Pathol 54:409–413

    PubMed  CAS  Google Scholar 

  • DiFiglia M, Sapp E, Chase K et al (1995) Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14:1075–1081

    Article  PubMed  CAS  Google Scholar 

  • DiFiglia M, Sapp E, Chase KO et al (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990–1993

    Article  PubMed  CAS  Google Scholar 

  • DiProspero NA, Chen EY, Charles V et al (2004) Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements. J Neurocytol 33:517–533

    Article  PubMed  Google Scholar 

  • Dompierre JP, Godin JD, Charrin BC et al (2007) Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci 27:3571–3583

    Article  PubMed  CAS  Google Scholar 

  • Drew CJ, Kyd RJ, Morton AJ (2007) Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal. Hum Mol Genet 16:2288–2305

    Article  PubMed  CAS  Google Scholar 

  • Dure LS 4th, Young AB, Penney JB (1991) Excitatory amino acid binding sites in the caudate nucleus and frontal cortex of Huntington’s disease. Ann Neurol 30:785–793

    Article  PubMed  Google Scholar 

  • Eastwood SL, Harrison PJ (2000) Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5:425–432

    Article  PubMed  CAS  Google Scholar 

  • Eastwood, SL, Cotter D, Harrison PJ (2001) Cerebellar synaptic protein expression in schizophrenia. Neuroscience 105:219–229

    Article  PubMed  CAS  Google Scholar 

  • Eastwood SL, Harrison PJ (2001) Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull 55:569–578

    Article  PubMed  CAS  Google Scholar 

  • Eastwood SL (2004) The synaptic pathology of schizophrenia: is aberrant neurodevelopment and plasticity to blame? Int Rev Neurobiol 59:47–72

    Article  PubMed  CAS  Google Scholar 

  • Eastwood SL, Harrison PJ (2005) Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons. Schizophr Res 73:159–172

    Article  PubMed  CAS  Google Scholar 

  • Edwardson JM, Wang CT, Gong B et al (2003) Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II. J Biol Chem 278:30849–30853

    Article  PubMed  CAS  Google Scholar 

  • Engelender S, Sharp AH, Colomer V et al (1997) Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin. Hum Mol Genet 6:2205–2212

    Article  PubMed  CAS  Google Scholar 

  • Engqvist-Goldstein AE, Kessels MM, Chopra VS et al (1999) An actin-binding protein of the Sla2/Huntingtin interacting protein 1 family is a novel component of clathrin-coated pits and vesicles. J Cell Biol 147:1503–1518

    Article  PubMed  CAS  Google Scholar 

  • Fan MM, Raymond LA (2007) N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease. Prog Neurobiol 81:272–293

    Article  PubMed  CAS  Google Scholar 

  • Faull RL, Waldvogel HJ, Nicholson LF et al (1993) The distribution of GABAA-benzodiazepine receptors in the basal ganglia in Huntington’s disease and in the quinolinic acid-lesioned rat. Prog Brain Res 99:105–123

    Article  PubMed  CAS  Google Scholar 

  • Ferrante RJ, Kowall NW, Richardson EP 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

    PubMed  CAS  Google Scholar 

  • Fiebig KM, Rice LM, Pollack E et al (1999) Folding intermediates of SNARE complex assembly. Nat Struct Biol 6:117–123

    Article  PubMed  CAS  Google Scholar 

  • Folstein SE, Jensen B, Leigh RJ et al (1983) The measurement of abnormal movement: methods developed for Huntington’s disease. Neurobehav Toxicol Teratol 5:605–609

    PubMed  CAS  Google Scholar 

  • Freeman W, Morton AJ (2004a) Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington’s Disease mutation. Brain Res Bull 63:45–55

    Article  PubMed  CAS  Google Scholar 

  • Freeman W, Morton AJ (2004b) Differential messenger RNA expression of complexins in mouse brain. Brain Res Bull 63:33–44

    Article  PubMed  CAS  Google Scholar 

  • Gibson HE, Reim K, Brose N et al (2005) A similar impairment in CA3 mossy fibre LTP in the R6/2 mouse model of Huntington’s disease and in the complexin II knockout mouse. Eur J Neurosci 22:1701–1712

    Article  PubMed  Google Scholar 

  • Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27:2803–2820

    Article  PubMed  Google Scholar 

  • Giraudo CG, Eng WS, Melia TJ et al (2006) A clamping mechanism involved in SNARE-dependent exocytosis. Science 283:21211–21219

    Google Scholar 

  • Glass M, Faull RL, Dragunow M (1993) Loss of cannabinoid receptors in the substantia nigra in Huntington’s disease. Neuroscience 56:523–527

    Article  PubMed  CAS  Google Scholar 

  • Glass M, Dragunow M, Faull RL (2000) The pattern of neurodegeneration in Huntington’s disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington’s disease. Neuroscience 97:505–519

    Article  PubMed  CAS  Google Scholar 

  • Glass M (2001) The role of cannabinoids in neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 25:743–765

    Article  PubMed  CAS  Google Scholar 

  • Glynn D, Bortnick RA, Morton AJ (2003) Complexin II is essential for normal neurological function in mice. Hum Mol Genet 12:2431–3448

    Article  PubMed  CAS  Google Scholar 

  • Glynn D, Drew CJ, Reim K et al (2005) Profound ataxia in Complexin 1 knockout mice masks a complex phenotype that includes exploratory and habituation deficits. Hum Mol Genet 14:2369–2385

    Article  PubMed  CAS  Google Scholar 

  • Glynn D, Morton AJ (2006) Deficits in information processing and social behaviours in the Complexin 2 knockout mouse. FENS Abstract 3:A458

    Google Scholar 

  • Glynn D, Sizemore RJ, Morton AJ (2007a) Early motor development is abnormal in complexin 1 knockout mice. Neurobiol Dis 25:483–495

    Article  PubMed  CAS  Google Scholar 

  • Glynn D, Reim K, Brose N et al (2007b) Depletion of Complexin II does not affect disease progression in a mouse model of Huntington’s disease (HD); support for role for complexin II in behavioural pathology in a mouse model of HD. Brain Res Bull 72:108–120

    Article  PubMed  CAS  Google Scholar 

  • Graveland GA, Williams RS, DiFiglia M (1985) Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease. Science 227:770–773

    Article  PubMed  CAS  Google Scholar 

  • Gray M, Shirasaki DI, Cepeda C et al (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28:6182–6195

    Article  PubMed  CAS  Google Scholar 

  • Gunawardena S, Her LS, Brusch RG et al (2003) Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40:25–40

    Article  PubMed  CAS  Google Scholar 

  • Gunawardena S, Goldstein LS (2005) Polyglutamine diseases and transport problems: deadly traffic jams on neuronal highways. Arch Neurol 62:46–51

    Article  PubMed  Google Scholar 

  • Hansson O, Guatteo E, Mercuri NB et al (2001) 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. Eur J Neurosci 14:1492–1504

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, Eastwood SL (1998) Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 352:1669–1673

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, Eastwood SL (2000) Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5:425–532

    Article  PubMed  Google Scholar 

  • Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858

    Article  PubMed  CAS  Google Scholar 

  • Hazell AS, Wang C (2005) Downregulation of complexin I and complexin II in the medial thalamus is blocked by N-acetylcysteine in experimental Wernicke’s encephalopathy. J Neurosci Res 79:200–207

    Article  PubMed  CAS  Google Scholar 

  • Hedreen JC, Peyser CE, Folstein SE et al (1991) Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci Lett 133:257–261

    Article  PubMed  CAS  Google Scholar 

  • Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479

    Article  PubMed  CAS  Google Scholar 

  • Hilditch-Maguire P, Trettel F, Passani LA et al (2000) Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum Mol Genet 9:2789–2797

    Article  PubMed  CAS  Google Scholar 

  • Hiley CR, Bird ED (1974) Decreased muscarinic receptor concentration in post-mortem brain in Huntington’s chorea. Brain Res 80:355–358

    Article  PubMed  CAS  Google Scholar 

  • Hodgson JG, Agopyan N, Gutekunst CA et al (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23:181–192

    Article  PubMed  CAS  Google Scholar 

  • Holthoff VA, Koeppe RA, Frey KA et al (1993) Positron emission tomography measures of benzodiazepine receptors in Huntington’s disease. Ann Neurol 34:76–81

    Article  PubMed  CAS  Google Scholar 

  • The 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

    Article  Google Scholar 

  • Huntwork S, Littleton JT (2007) A complexin fusion clamp regulates spontaneous neurotransmitter release and synaptic growth. Nat Neurosci 10:1235–1237

    Article  PubMed  CAS  Google Scholar 

  • Jahn R, Südhof TC (1999) Membrane fusion and exocytosis. Annu Rev Biochem 68:863–911

    Article  PubMed  CAS  Google Scholar 

  • Jahn R, Scheller RH (2006) SNAREs-engines for membrane fusion. Nat Rev Mol Cell Biol 7:631–643

    Article  PubMed  CAS  Google Scholar 

  • Jana NR, Zemskov EA, Wang GH et al (2001) Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum Mol Genet 10:1049–1059

    Article  PubMed  CAS  Google Scholar 

  • Jason GW, Pajurkova EM, Suchowersky OEA (1988) Presymptomatic neuropsychological impairment in Huntington’s disease. Arch Neurol 45:769–773

    Article  PubMed  CAS  Google Scholar 

  • Kalchman MA, Koide HB, McCutcheon K et al (1997) HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet 16:44–53

    Article  PubMed  CAS  Google Scholar 

  • Kittler JT, Thomas P, Tretter V et al (2004) Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking. Proc Natl Acad Sci U S A 101:12736–12741

    Article  PubMed  CAS  Google Scholar 

  • Klapstein GJ, Fisher RS, Zanjani H et al (2001) Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington’s disease transgenic mice. J Neurophysiol 86:2667–2677

    PubMed  CAS  Google Scholar 

  • Kremer HP, Roos RA, Dingjan G et al (1990) Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J Neuropathol Exp Neurol 49:371–382

    Article  PubMed  CAS  Google Scholar 

  • Kung VW, Hassam R, Morton AJ, Jones S (2007) Neuroscience 146:1571–1580

    Article  PubMed  CAS  Google Scholar 

  • Laforet GA, Sapp E, Chase K 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

    PubMed  CAS  Google Scholar 

  • Lastres-Becker I, Fezza F, Cebeira M et al (2001) Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington’s disease. Neuroreport 12:2125–2129

    Article  PubMed  CAS  Google Scholar 

  • Lastres-Becker I, Gomez M, De Miguel R et al (2002) Loss of cannabinoid CB(1) receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington’s disease. Neurotox Res 4:601–608

    Article  PubMed  CAS  Google Scholar 

  • Lawrence AD, Sahakian BJ, Hodges JR et al (1996) Executive and mnemonic functions in early Huntington’s disease. Brain 119:1633–1645

    Article  PubMed  Google Scholar 

  • Lawrence AD, Weeks RA, Brooks DJ et al (1998) The relationship between striatal dopamine receptor binding and cognitive performance in Huntington’s disease. Brain 121:1343–1355

    Article  PubMed  Google Scholar 

  • Lawrence AD, Sahakian BJ, Rogers RD et al (1999) Discrimination, reversal, and shift learning in Huntington’s disease mechanisms of impaired response selection. Neuropsychologia 37:1359–1374

    Article  PubMed  CAS  Google Scholar 

  • Lee WC, Yoshihara M, Littleton JT (2004) Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington’s disease. Proc Natl Acad Sci U S A 101:3224–3229

    Article  PubMed  CAS  Google Scholar 

  • Legendre-Guillemin V, Metzler M, Charbonneau M et al (2002) HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. J Biol Chem 277:19897–19904

    Article  PubMed  CAS  Google Scholar 

  • Levine MS, Klapstein GJ, Koppel A et al (1999) Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knockin mouse models of Huntington’s disease. J Neurosci Res 58:515–532

    Article  PubMed  CAS  Google Scholar 

  • Li XJ, Li SH, Sharp AH et al (1995) A huntingtin-associated protein enriched in brain with i­mplications for pathology. Nature 378:398–402

    Article  PubMed  CAS  Google Scholar 

  • Li SH, Gutekunst CA, Hersch SM et al (1998) Interaction of huntingtin-associated protein with dynactin P150Glued. J Neurosci 18:1261–1269

    PubMed  CAS  Google Scholar 

  • Li H, Li SH, Yu ZX et al (2001) Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice. J Neurosci 21:8473–8481

    PubMed  CAS  Google Scholar 

  • Li Y, Chin LS, Levey AI et al (2002) Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking. J Biol Chem 277:28212–28221

    Article  PubMed  CAS  Google Scholar 

  • Li JY, Plomann M, Brundin P (2003) Huntington’s disease: a synaptopathy? Trends Mol Med 9:414–420

    Article  PubMed  CAS  Google Scholar 

  • Li L, Murphy TH, Hayden MR et al (2004) Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease. J Neurophysiol 92:2738–2746

    Article  PubMed  CAS  Google Scholar 

  • Lievens JC, Woodman B, Mahal A et al (2001) Impaired glutamate uptake in the R6 Huntington’s disease transgenic mice. Neurobiol Dis 8:807–821

    Article  PubMed  CAS  Google Scholar 

  • Lin RC, Scheller RH (2000) Mechanisms of synaptic vesicle exocytosis. Annu Rev Cell Dev Biol 16:1–49

    Article  Google Scholar 

  • Lione LA, Carter RJ, Hunt MJ et al (1999) Selective discrimination learning impairments in mice expressing the human Huntington’s disease mutation. J Neurosci 19:10428–10437

    PubMed  CAS  Google Scholar 

  • London ED, Yamamura HI, Bird ED et al (1981) Decreased receptor-binding sites for kainic acid in brains of patients with Huntington’s disease. Biol Psychiatry 16:155–162

    PubMed  CAS  Google Scholar 

  • Luthi-Carter R, Strand A, Peters NL et al (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9:1259–1271

    Article  PubMed  CAS  Google Scholar 

  • Lynch G, Kramar EA, Rex CS et al (2007) Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington’s disease. J Neurosci 27:4424–4434

    Article  PubMed  CAS  Google Scholar 

  • Maccarrone M, Battista N, Centonze D (2007) The endocannabinoid pathway in Huntington’s disease: a comparison with other neurodegenerative diseases. Prog Neurobiol 81:349–379

    Article  PubMed  CAS  Google Scholar 

  • Mangiarini L, Sathasivam K, Seller M et al (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

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease. Neuroscience 3:697–706

    Article  Google Scholar 

  • Mazarakis NK, Cybulska-Klosowicz A, Grote H et al (2005) Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington’s disease mice. J Neurosci 25:3059–3066

    Article  PubMed  CAS  Google Scholar 

  • McCaw EA, Hu H, Gomez GT et al (2004) Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington’s disease transgenic mice. Eur J Biochem 271:4909–4920

    Article  PubMed  CAS  Google Scholar 

  • McMahon HJ, Missler M, Li C et al (1995) Complexins: cytosolic proteins that regulate SNAP receptor function. Cell 83:111–119

    Article  PubMed  CAS  Google Scholar 

  • Melia TJ Jr (2007) Putting the clamps on membrane fusion: how complexin sets the stage for calcium-mediated exocytosis. FEBS Lett 581:2131–2139

    Article  PubMed  CAS  Google Scholar 

  • Menalled LB, Chesselet MF (2002) Mouse models of Huntington’s disease. Trends Pharmacol Sci 23:32–39

    Article  PubMed  CAS  Google Scholar 

  • Menalled LB (2005) Knock-in mouse models of Huntington’s disease. NeuroRx 2:465–470

    Article  PubMed  Google Scholar 

  • Metzler M, Li B, Gan L et al (2003) Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. EMBO J 22:3254–3266

    Article  PubMed  CAS  Google Scholar 

  • Milnerwood AJ, Cummings DM, Dallerac GM et al (2006) Early development of aberrant synaptic plasticity in a mouse model of Huntington’s disease. Hum Mol Genet 15:1690–1703

    Article  PubMed  CAS  Google Scholar 

  • Milnerwood AJ, Raymond LA (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

    Article  PubMed  CAS  Google Scholar 

  • Mizuno H, Shibayama H, Tanaka F et al (2000) An autopsy case with clinically and molecular genetically diagnosed Huntington’s disease with only minimal non-specific neuropathological findings. Clin Neuropathol 19:94–103

    PubMed  CAS  Google Scholar 

  • Modregger J, DiProspero NA, Charles V et al (2002) PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington’s disease brains. Hum Mol Genet 11:2547–2558

    Article  PubMed  CAS  Google Scholar 

  • Modregger J, Schmidt AA, Ritter B et al (2003) Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1. J Biol Chem 278:4160–4167

    Article  PubMed  CAS  Google Scholar 

  • Montoya A, Price BH, Menear M et al (2006) Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci 31:21–29

    PubMed  Google Scholar 

  • Morfini GA, You YM, Pollema SL et al (2009) Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci 12:864–871

    Article  PubMed  CAS  Google Scholar 

  • Morton AJ, Lagan MA, Skepper JN et al (2000) Progressive formation of inclusions in the striatum and hippocampus of mice transgenic for the human Huntington’s disease mutation. J Neurocytol 29:679–702

    Article  PubMed  CAS  Google Scholar 

  • Morton AJ, Edwardson JM (2001) Progressive depletion of CPLXII in a transgenic mouse model of Huntington’s disease. J Neurochem 76:166–172

    Article  PubMed  CAS  Google Scholar 

  • Morton AJ, Faull RLM, Edwardson JM (2001) Abnormalities in the synaptic vesicle fusion machinery in Huntington’s disease. Brain Res Bull 56:111–117

    Article  PubMed  CAS  Google Scholar 

  • Morton AJ, Hunt MJ, Hodges AK et al (2005) A combination drug therapy improves cognition and reverses gene expression changes in a mouse model of Huntington’s disease. Eur J Neurosci 21:855–870

    Article  PubMed  Google Scholar 

  • Murphy KP, Carter RJ, Lione LA 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

    PubMed  CAS  Google Scholar 

  • Myers RH, Vonsattel JP, Stevens TJ et al (1988) Clinical and neuropathologic assessment of severity in Huntington’s disease. Neurology 38:341–347

    Article  PubMed  CAS  Google Scholar 

  • Nicniocaill B, Haraldsson B, Hansson O et al (2001) Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice. Eur J Neurosci 13:206–210

    Article  PubMed  CAS  Google Scholar 

  • Nithianantharajah, J, Barkus, C, Murphy, M et al (2008) Gene–environment interactions modulating cognitive function and molecular correlates of synaptic plasticity in Huntington’s disease transgenic mice. Neurobiol Dis 29:490–504

    Article  PubMed  CAS  Google Scholar 

  • Ono S, Baux G, Sekiguchi M et al (1998) Regulatory roles of complexins in neurotransmitter release from mature presynaptic nerve terminals. Eur J Neurosci 10:2143–2152

    Article  PubMed  CAS  Google Scholar 

  • Pabst S, Margittai M, Vainius D et al (2002) Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis. J Biol Chem 277:7838–7848

    Article  PubMed  CAS  Google Scholar 

  • Pang, TY, Stam, NC, Nithianantharajah, J et al (2006) Differential effects of voluntary physical exercise on behavioural and brain-derived neurotrophic factor expression deficits in Huntington’s disease transgenic mice. Neuroscience 141:569–584

    Article  PubMed  CAS  Google Scholar 

  • Patel S, Sinha A, Singh MP (2007) Identification of differentially expressed proteins in striatum of maneb-and paraquat-induced Parkinson’s disease phenotype in mouse. Neurotoxicol Teratol 29:578–585

    Article  PubMed  CAS  Google Scholar 

  • Pavese N, Andrews TC, Brooks DJ et al (2003) Progressive striatal and cortical dopamine receptor dysfunction in Huntington’s disease: a PET study. Brain 126:1127–1135

    Article  PubMed  Google Scholar 

  • Perry TL, Hansen S, Kloster M (1973) Huntington’s chorea: deficiency of gamma aminobutyric acid in brain. N Engl J Med 288:337–342

    Article  PubMed  CAS  Google Scholar 

  • Petersen A, Puschban Z, Lotharius J et al (2002) Evidence for dysfunction of the nigrostriatal pathway in the R6/1 line of transgenic Huntington’s disease mice. Neurobiol Dis 11:134–146

    Article  PubMed  CAS  Google Scholar 

  • Pisani A, Bernardi G, Ding J et al (2007) Re-emergence of striatal cholinergic interneurons in movement disorders. Trends Neurosci 30:545–553

    Article  PubMed  CAS  Google Scholar 

  • Politis M, Pavese N, Tai YF et al (2008) Hypothalamic involvement in Huntington’s disease: an in vivo PET study. Brain 131:2860–2869

    Article  PubMed  Google Scholar 

  • Reddy PH, Williams M, Tagle DA (1999) Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci 22:248–255

    Article  PubMed  CAS  Google Scholar 

  • Reed NA, Cai D, Blasius TL et al (2006) Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol 16:2166–2172

    Article  PubMed  CAS  Google Scholar 

  • Reim K, Mansour M, Varoqueaux F et al (2001) Complexins regulate a late step in Ca2+-dependent neurotransmitter release Cell 104:71–81

    Article  PubMed  CAS  Google Scholar 

  • Reisine TD, Fields JZ, Stern LZ et al (1977) Alterations in dopaminergic receptors in Huntington’s disease. Life Sci 21:1123–1128

    Article  PubMed  CAS  Google Scholar 

  • Reynolds GP, Pearson SJ (1987) Decreased glutamic acid and increased 5-hydroxytryptamine in Huntington’s disease brain. Neurosci Lett 78:233–238

    Article  PubMed  CAS  Google Scholar 

  • Ribchester RR, Thomson D, Wood NI et al (2004) Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington’s disease mutation. Eur J Neurosci 20:3092–3114

    Article  PubMed  Google Scholar 

  • Richfield EK, Herkenham M (1994) Selective vulnerability in Huntington’s disease: preferential loss of cannabinoid receptors in lateral globus pallidus. Ann Neurol 36:577–584

    Article  PubMed  CAS  Google Scholar 

  • Rizo J, Südhof TC (2002) SNAREs and munc-18 in synaptic vesicle fusion. Nat Rev Neurosci 3:641–653

    PubMed  CAS  Google Scholar 

  • Rong J, McGuire JR, Fang ZH 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

    Article  PubMed  CAS  Google Scholar 

  • Rosenmund C, Rettig J, Brose N (2003) Molecular mechanisms of active zone function. Curr Opin Neurobiol 13:509–519

    Article  PubMed  CAS  Google Scholar 

  • Ross CA, Wood JD, Schilling G et al (1999) Polyglutamine pathogenesis. Philos Trans R Soc Lond B Biol Sci 354:1005–1011

    Article  PubMed  CAS  Google Scholar 

  • Sapp E, Penney J, Young A et al (1999) Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease. J Neuropathol Exp Neurol 58:165–173

    Article  PubMed  CAS  Google Scholar 

  • Sawada K, Young CE, Barr AM et al (2002) Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness. Mol Psychiatry 7:484–492

    Article  PubMed  CAS  Google Scholar 

  • Sawada K, Barr AM, Nakamura M et al (2005) Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Arch Gen Psychiatry 62:263–272

    Article  PubMed  CAS  Google Scholar 

  • Schaub JR, Lu X, Doneske B et al (2006) Hemifusion arrest by complexin is relieved by Ca2+-synaptotagmin I. Nat Struct Mol Biol 13:748–750

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298:789–791

    Article  PubMed  CAS  Google Scholar 

  • Shehadeh J, Fernandes HB, Zeron Mullins MM et al (2006) Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 21:392–403

    Article  PubMed  CAS  Google Scholar 

  • Shoulson I, Fahn S (1979) Huntington’s disease: clinical care and evaluation. Neurology 29:1–3

    Article  PubMed  CAS  Google Scholar 

  • Sinadinos C, Burbidge-King T, Soh D et al (2009) Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons. Neurobiol Dis 34:389–395

    Article  PubMed  CAS  Google Scholar 

  • Singaraja RR, Hadano S, Metzler M et al (2002) HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum Mol Genet 11:2815–2828

    Article  PubMed  CAS  Google Scholar 

  • Sittler A, Walter S, Wedemeyer N et al (1998) SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates. Mol Cell 2:427–436

    Article  PubMed  CAS  Google Scholar 

  • Smith R, Brundin P, Li JY (2005) Synaptic dysfunction in Huntington’s disease: a new perspective. Cell Mol Life Sci 62:1901–1912

    Article  PubMed  CAS  Google Scholar 

  • Smith R, Chung H, Rundquist S et al (2006) Cholinergic neuronal defect without cell loss in Huntington’s disease. Hum Mol Genet 15:3119–3131

    Article  PubMed  CAS  Google Scholar 

  • Smith R, Klein P, Koc-Schmitz Y et al (2007) Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington’s disease. J Neurochem 103:115–123

    PubMed  CAS  Google Scholar 

  • Snell RG, MacMillan JC, Cheadle JP et al (1993) Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington’s disease. Nat Genet 4:393–397

    Article  PubMed  CAS  Google Scholar 

  • Sollner T, Bennett MK, Whiteheart SW et al (1993) A protein assembly-dissambly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation and fusion. Cell 75:2213–2217

    Article  Google Scholar 

  • Spires TL, Grote HE, Garry S et al (2004) Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington’s disease transgenic mice. Eur J Neurosci 19:2799–2807

    Article  PubMed  Google Scholar 

  • Spokes EG (1980) Neurochemical alterations in Huntington’s chorea: a study of post-mortem brain tissue. Brain 103:179–210

    Article  PubMed  CAS  Google Scholar 

  • Stack EC, Kubilus JK, Smith KM et al (2005) Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington’s disease transgenic mice. J Comp Neurol 490:354–370

    Article  PubMed  Google Scholar 

  • Starling AJ, Andre VM, Cepeda C et al (2005) Alterations in N-methyl-D-aspartate receptor sensitivity and magnesium blockade occur early in development in the R6/2 mouse model of Huntington’s disease. J Neurosci Res 82:377–386

    Article  PubMed  CAS  Google Scholar 

  • Steward LJ, Bufton KE, Hopkins PC et al (1993) Reduced levels of 5-HT3 receptor recognition sites in the putamen of patients with Huntington’s disease. Eur J Pharmacol 242:137–143

    Article  PubMed  CAS  Google Scholar 

  • Strauss ME, Brandt J (1990) Are there neuropsychologic manifestations of the gene for Huntington’s disease in asymptomatic, at-risk individuals? Arch Neurol 47:905–908

    Article  PubMed  CAS  Google Scholar 

  • Südhof T (1995) The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 375:645–653

    Article  PubMed  Google Scholar 

  • Südhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27:509–547

    Article  PubMed  CAS  Google Scholar 

  • Szebenyi G, Morfini GA, Babcock A et al (2003) Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 40:41–52

    Article  PubMed  CAS  Google Scholar 

  • Tang TS, Tu H, Chan EY et al (2003) Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 39:227–239

    Article  PubMed  CAS  Google Scholar 

  • Tannenberg RK, Scott HL, Tannenberg AE et al (2006) Selective loss of synaptic proteins in Alzheimer’s disease: Evidence for an increased severity with APOE varepsilon4. Neurochem Int 49:631–639

    Article  PubMed  CAS  Google Scholar 

  • Tippett LJ, Waldvogel HJ, Thomas SJ et al (2007) Striosomes and mood dysfunction in Huntington’s disease. Brain 130:206–221

    Article  PubMed  Google Scholar 

  • Tokumaru H, Umayahara K, Pellegrini LL et al (2001) SNARE Complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis. Cell 104:421–432

    Article  PubMed  CAS  Google Scholar 

  • Trushina E, Dyer RB, Badger JD, 2nd et al (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24:8195–8209

    Article  PubMed  CAS  Google Scholar 

  • Usdin MT, Shelbourne PF, Myers RM et al (1999) Impaired synaptic plasticity in mice carrying the Huntington’s disease mutation. Hum Mol Genet 8:839–846

    Article  PubMed  CAS  Google Scholar 

  • van Oostrom JC, Maguire RP, Verschuuren-Bemelmans CC et al (2005) Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease. Neurology 65:941–943

    Article  PubMed  CAS  Google Scholar 

  • Velier J, Kim MT, Schwarz C et al (1998) Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways. Exp Neurol 152:34–40

    Article  PubMed  CAS  Google Scholar 

  • Vetter JM, Jehle T, Heinemeyer J et al (2003) Mice transgenic for exon 1 of Huntington’s disease: properties of cholinergic and dopaminergic pre-synaptic function in the striatum. J Neurochem 85:1054–1063

    Article  PubMed  CAS  Google Scholar 

  • Vonsattel JP, Myers RH, Stevens TJ et al (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44:559–577

    Article  PubMed  CAS  Google Scholar 

  • Vonsattel JPG, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57:369–384

    Article  PubMed  CAS  Google Scholar 

  • Wade A, Jacobs P, Morton AJ (2008) Atrophy and degeneration in sciatic nerve of presymptomatic mice carrying the Huntington’s disease mutation. Brain Res 1188:61–68

    Article  PubMed  CAS  Google Scholar 

  • Waeber C, Palacios JM (1989) Serotonin-1 receptor binding sites in the human basal ganglia are decreased in Huntington’s chorea but not in Parkinson’s disease: a quantitative in vitro autoradiography study. Neuroscience 32:337–347

    Article  PubMed  CAS  Google Scholar 

  • Waeber C, Rigo M, Chinaglia G et al (1991) Beta-adrenergic receptor subtypes in the basal ganglia of patients with Huntington’s chorea and Parkinson’s disease. Synapse 8:270–280

    Article  PubMed  CAS  Google Scholar 

  • Walsh DM, Klyubin I, Fadeeva JV et al (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–539

    Article  PubMed  CAS  Google Scholar 

  • Wanderer J, Morton AJ (2007) Differential morphology and composition of inclusions in the R6/2 mouse and PC12 cell models of Huntington’s disease. Histochem Cell Biol 127:473–484

    Article  PubMed  CAS  Google Scholar 

  • Wang CE, Zhou H, McGuire JR et al (2008) Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J Cell Biol 181:803–816

    Article  PubMed  CAS  Google Scholar 

  • Wanker EE, Rovira C, Scherzinger E et al (1997) HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet 6:487–495

    Article  PubMed  CAS  Google Scholar 

  • Waterman-Storer CM, Karki SB, Kuznetsov SA et al (1997) The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proc Natl Acad Sci U S A 94:12180–12185

    Article  PubMed  CAS  Google Scholar 

  • Weeks RA, Cunningham VJ, Piccini P et al (1997) 11C-diprenorphine binding in Huntington’s disease: a comparison of region of interest analysis with statistical parametric mapping. J Cereb Blood Flow Metab 17:943–949

    Article  PubMed  CAS  Google Scholar 

  • Witzmann FA, Li J, Strother WN et al (2003) Innate differences in protein expression in the nucleus accumbens and hippocampus of inbred alcohol-preferring and -nonpreferring rats. Proteomics 3:1335–1344

    Article  PubMed  CAS  Google Scholar 

  • Wong EH, Reynolds GP, Bonhaus DW et al (1996) Characterization of [3H]GR 113808 binding to 5-HT4 receptors in brain tissues from patients with neurodegenerative disorders. Behav Brain Res 73:249–252

    Article  PubMed  CAS  Google Scholar 

  • Wyttenbach A, Carmichael J, Swartz J et al (2000) Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington’s disease. Proc Natl Acad Sci U S A 97:2898–2903

    Article  PubMed  CAS  Google Scholar 

  • Xue M, Reim K, Chen X et al (2007) Distinct domains of complexin I differentially regulate neurotransmitter release. Nat Struct Mol Biol 14:949–958

    Article  PubMed  CAS  Google Scholar 

  • Yi JH, Hoover R, McIntosh TK et al (2006) Early, transient increase in complexin I and complexin II in the cerebral cortex following traumatic brain injury is attenuated by N-acetylcysteine. J Neurotrauma 23:86–96

    Article  PubMed  Google Scholar 

  • Young AB, Shoulson I, Penney JB (1986) Huntington’s disease in Venezuela: neurologic feature and functional decline. Neurology 36:244–249

    Article  PubMed  CAS  Google Scholar 

  • Young AB, Greenamyre JT, Hollingsworth Z et al (1988) NMDA receptor losses in putamen from patients with Huntington’s disease. Science 241:981–983

    Article  PubMed  CAS  Google Scholar 

  • Zabel C, Sagi D, Kaindl AM et al (2006) Comparative proteomics in neurodegenerative and non-neurodegenerative diseases suggest nodal point proteins in regulatory networking. J Proteome Res 5:1948–1958

    Article  PubMed  CAS  Google Scholar 

  • Zechner U, Scheel S, Hemberger M et al (1998) Characterization of the mouse Src homology 3 domain gene Sh3d2c on Chr 7 demonstrates coexpression with huntingtin in the brain and identifies the processed pseudogene Sh3d2c-ps1 on Chr 2. Genomics 54:505–510

    Article  PubMed  CAS  Google Scholar 

  • Zeron MM, Chen N, Moshaver A et al (2001) Mutant huntingtin enhances excitotoxic cell death. Mol Cell Neurosci 17:41–53

    Article  PubMed  CAS  Google Scholar 

  • Zeron MM, Hansson O, Chen N (2002) Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease. Neuron 33:849–860

    Article  PubMed  CAS  Google Scholar 

  • Zeron MM, Fernandes HB, Krebs C et al (2004) Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington’s disease. Mol Cell Neurosci 25:469–479

    Article  PubMed  CAS  Google Scholar 

  • Zink M, Vollmayr B, Gebicke-Haerter PJ et al (2007) Reduced expression of complexins I and II in rats bred for learned helplessness. Brain Res 1144:202–208

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK

    A. Jennifer Morton

Authors
  1. Dervila Glynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Jennifer Morton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Jennifer Morton .

Editor information

Editors and Affiliations

  1. School of Biological Sciences, University of Southampton, Life Science Building (B85), SO17 1BJ, Southampton, SO16 7PX, United Kingdom

    Andreas Wyttenbach

  2. School of Biological Sciences, University of Southampton, Life Science Building (B85), SO17 1BJ, Southampton, SO16 7PX, United Kingdom

    Vincent O'Connor

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Glynn, D., Morton, A.J. (2011). Synaptic Dysfunction in Huntington’s Disease. In: Wyttenbach, A., O'Connor, V. (eds) Folding for the Synapse. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7061-9_12

Download citation

Publish with us

Policies and ethics

Search

Navigation