Synaptic and cognitive abnormalities in mouse models of Down syndrome: Exploring genotype-phenotype relationships

Journal of Comparative Neurology

Volumn 504, Issue 4, 2007, Pages 329-345

  Belichenko, Pavel V ^a   Kleschevnikov, Alexander M ^a   Salehi, Ahmad ^a   Epstein, Charles J ^b   Mobley, William C ^c  

^a STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NONE

Author keywords

Behavior; Down syndrome; LTP; Morphometry; Spines; Synapses; Ts1Cje

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR BLOCKING AGENT; PICROTOXIN;

ANIMAL TISSUE; ARTICLE; BRAIN SIZE; CHROMOSOME 21; COGNITIVE DEFECT; CONTROLLED STUDY; DENTATE GYRUS; DOWN SYNDROME; GENOTYPE; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SYNAPSE;

ANIMALS; BRAIN; COGNITION DISORDERS; DENDRITIC SPINES; DENTATE GYRUS; DISEASE MODELS, ANIMAL; DOWN SYNDROME; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; LONG-TERM POTENTIATION; MALE; MAZE LEARNING; MICE; MICE, MUTANT STRAINS; NEURAL INHIBITION; NEURAL PATHWAYS; ORGAN SIZE; PHENOTYPE; RECEPTORS, GABA-A; SYNAPSES; TRISOMY;

EID: 34548795562     PISSN: 00219967     EISSN: 10969861     Source Type: Journal    
DOI: 10.1002/cne.21433     Document Type: Article

References (84)

1. Agarwala KL, Ganesh S, Suzuki T, Akagi T, Kaneko K, Amano K, Tsutsumi Y, Yamaguchi K, Hashikawa T, Yamakawa K. 2001. Dscam is associated with axonal and dendritic features of neuronal cells. J Neurosci Res 66:337-346.
2. Ann KJ, Jeong HK, Choi HS, Ryoo SR, Kim YJ, Goo JS, Choi SY, Han JS, Ha I, Song WJ. 2006. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 22:463-472.
3. Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J, Oset M, Gonzalez JR, Florez J, Fillat C, Estivill X. 2001. Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet 10:1915-1923.
4. Amano K, Sago H, Uchikawa C, Suzuki T, Kotliarova SE, Nukina N, Epstein CJ, Yamakawa K. 2004. Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome. Hum Mol Genet 13:1333-1340.
5. Antonarakis SE, Warren AC, McCormick MK, Lewis JG, Hieter PA, Chakravarti A. 1989. Molecular mapping of chromosome 21 and the region responsible for Down syndrome. Prog Clin Biol Res 311:29-43.
6. Arai Y, Ijuin T, Takenawa T, Becker LE, Takashima S. 2002. Excessive expression of synaptojanin in brains with Down syndrome. Brain Dev 24:67-72.
7. Argellati F, Massone S, d'Abramo C, Marinari UM, Pronzato MA, Domenicotti C, Ricciarelli R. 2006. Evidence against the overexpression of APP in Down syndrome. IUBMB Life 58:103-106.
8. Armstrong RA. 1994. Differences in beta-amyloid (beta/A4) deposition in human patients with Down's syndrome and sporadic Alzheimer's disease. Neurosci Lett 169:133-136.
9. Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, Neilson JR, Chen L, Heit JJ, Kim SK, Yamasaki N, Miyakawa T, Francke U, Graef IA, Crabtree GR. 2006. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441:595-600.
10. Bar-Peled O, Korkotian E, Segal M, Groner Y. 1996. Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons. Proc Natl Acad Sci U S A 93:8530-8535.
11. Belichenko PV, Masliah E, Kleschevnikov AM, Villar AJ, Epstein CJ, Salehi A, Mobley WC. 2004. Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome. J Comp Neurol 480:281-298.
12. Bellocchio EE, Reimer RJ, Fremeau RT, Jr., Edwards RH. 2000. Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 289:957-960.
13. Beyreuther K, Pollwein P, Multhaup G, Monning U, Konig G, Dyrks T, Schubert W, Masters CL. 1993. Regulation and expression of the Alzheimer's beta/A4 amyloid protein precursor in health, disease, and Down's syndrome. Ann N Y Acad Sci 695:91-102.
14. Branchi I, Bichler Z, Minghetti L, Delabar JM, Malchiodi-Albedi F, Gonzalez MC, Chettouh Z, Nicolini A, Chabert C, Smith DJ, Rubin EM, Migliore-Samour D, Alleva E. 2004. Transgenic mouse in vivo library of human Down syndrome critical region 1: association between DYRK1A overexpression, brain development abnormalities, and cell cycle protein alteration. J Neuropathol Exp Neurol 63:429-440.
15. Brown JH, Johnson MH, Paterson SJ, Gilmore R, Longhi E, Karmiloff-Smith A. 2003. Spatial representation and attention in toddlers with Williams syndrome and Down syndrome. Neuropsychologia 41:1037-1046.
16. Cano E, Canellada A, Minami T, Iglesias T, Redondo JM. 2005. Depolarization of neural cells induces transcription of the Down syndrome critical region 1 isoform 4 via a calcineurin/nuclear factor of activated T cells-dependent pathway. J Biol Chem 280:29435-29443.
17. Casanova MF, Walker LC, Whitehouse PJ, Price DL. 1985. Abnormalities of the nucleus basalis in Down's syndrome. Ann Neurol 18:310-313.
18. Chrast R, Scott HS, Madani R, Huber L, Wolfer DP, Prinz M, Aguzzi A, Lipp HP, Antonarakis SE. 2000a. Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome. Hum Mol Genet 9:1853-1864.
19. Chrast R, Scott HS, Papasawas MP, Rossier C, Antonarakis ES, Barras C, Davisson MT, Schmidt C, Estivill X, Dierssen M, Pritchard M, Antonarakis SE. 2000b. The mouse brain transcriptome by SAGE: dfferences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals. Genome Res 10:2006-2021.
20. Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, Kilbridge JF, Carlson EJ, Epstein CJ, Mobley WC. 2001. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci U S A 98:10439-10444.
21. Costa AC, Grybko MJ. 2005. Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome. Neurosci Lett 382:317-322.
22. Delabar JM, Theophile D, Rahmani Z, Chettouh Z, Blouin JL, Prieur M, Noel B, Sinet PM. 1993. Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1:114-124.
23. Demas GE, Nelson RJ, Krueger BK, Yarowsky PJ. 1996. Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res 82:85-92.
24. Demas GE, Nelson RJ, Krueger BK, Yarowsky PJ. 1998. Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice. Behav Brain Res 90:199-201.
25. Deutsch S, Lyle R, Dermitzakis ET, Attar H, Subrahmanyan L, Gehrig C, Parand L, Gagnebin M, Rougemont J, Jongeneel CV, Antonarakis SE. 2005. Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes. Hum Mol Genet 14:3741-3749.
26. Dierssen M, Vallina IF, Baamonde C, Garcia-Calatayud S, Lumbreras MA, Florez J. 1997. Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Brain Res 749:238-244.
27. Dierssen M, Benavides-Piccione R, Martinez-Cue C, Estivill X, Florez J, Elston GN, DeFelipe J. 2003. Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: effects of environmental enrichment. Cereb Cortex 13:758-764.
28. Ema M, Ikegami S, Hosoya T, Mimura J, Ohtani H, Nakao K, Inokuchi K, Katsuki M, Fujii-Kuriyama Y. 1999. Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome. Hum Mol Genet 8:1409-1415.
29. Epstein CJ. 1990. The consequences of chromosome imbalance. Am J Med Genet Suppl 7:31-37.
30. Epstein CJ. 1993. The conceptual bases for the phenotypic mapping of conditions resulting from aneuploidy. Prog Clin Biol Res 384:1-18.
31. Epstein CJ, Avraham KB, Lovett M, Smith S, Elroy-Stein O, Rotman G, Bry C, Groner Y. 1987. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc Natl Acad Sci U S A 84:8044-8048.
32. Escorihuela RM, Fernandez-Teruel A, Vallina IF, Baamonde C, Lumbreras MA, Dierssen M, Tobena A, Florez J. 1995. A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neurosci Lett 199: 143-146.
33. Escorihuela RM, Vallina IF, Martinez-Cue C, Baamonde C, Dierssen M, Tobena A, Florez J, Fernandez-Teruel A. 1998. Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome. Neurosci Lett 247:171-174.
34. Fiala JC, Spacek J, Harris KM. 2002. Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Brain Res Rev 39: 29-54.
35. Gahtan E, Auerbach JM, Groner Y, Segal M. 1998. Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice. Eur J Neurosci 10:538-544.
36. Gardiner K, Fortna A, Bechtel L, Davisson MT. 2003. Mouse models of Down syndrome: how useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions. Gene 318:137-147.
37. Gerlai R. 2001. Behavioral tests of hippocampal function: simple paradigms complex problems. Behav Brain Res 125:269-277.
38. Granholm AC, Sanders LA, Crnic LS. 2000. Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome. Exp Neurol 161:647-663.
39. Granholm AC, Ford KA, Hyde LA, Bimonte HA, Hunter CL, Nelson M, Albeck D, Sanders LA, Mufson EJ, Crnic LS. 2002. Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome. Physiol Behav 77:371-385.
40. Harashima C, Jacobowitz DM, Stoffel M, Chakrabarti L, Haydar TF, Siarey RJ, Galdzicki Z. 2006a. Elevated expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in cerebellar unipolar brush cells of a Down syndrome mouse model. Cell Mol Neurobiol 26(4-6):719-734.
41. Harashima C, Jacobowitz DM, Witta J, Borke RC, Best TK, Siarey RJ, Galdzicki Z. 2006b. Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome. J Comp Neurol 494:815-833.
42. Harris-Cerruti C, Kamsler A, Kaplan B, Lamb B, Segal M, Groner Y. 2004. Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein [correction]. Eur J Neurosci 19:1174-1190.
43. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML. 2000. The DNA sequence of human chromosome 21. Nature 405:311-319.
44. Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC. 1996. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci U S A 93:13333-13338.
45. Hu D, Serrano F, Oury TD, Klann E. 2006. Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase. J Neurosci 26:3933-3941.
46. Hyde LA, Crnic LS. 2001. Age-related deficits in context discrimination learning in Ts65Dn mice that model Down syndrome and Alzheimer's disease. Behav Neurosci 115:1239-1246.
47. Kleschevnikov AM, Belichenko PV, Villar AJ, Epstein CJ, Malenka RC, Mobley WC. 2004. Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J Neurosci 24:8153-8160.
48. Korenberg JR, Chen XN, Schipper R, Sun Z, Gonsky R, Gerwehr S, Carpenter N, Daumer-C, Dignan P, Disteche C, et al. 1994. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A 91:4997-5001.
49. Lalonde R. 2002. The neurobiological basis of spontaneous alternation. Neurosci Biobehav Rev 26:91-104.
50. Levkovitz Y, Avignone E, Groner Y, Segal M. 1999. Upregulation of GABA neurotransmission suppresses hippocampal excitability and prevents long-term potentiation in transgenic superoxide dismutase-overexpressing mice. J Neurosci 19:10977-10984.
51. Lucente D, Chen HM, Shea D, Samec SN, Rutter M, Chrast R, Rossier C, Buckler A, Antonarakis SE, McCormick MK. 1995. Localization of 102 exons to a 2.5 Mb region involved in Down syndrome. Hum Mol Genet 4:1305-1311.
52. Luthi A, Di Paolo G, Cremona O, Daniell L, De Camilli P, McCormick DA. 2001. Synaptojanin 1 contributes to maintaining the stability of GABAergic transmission in primary cultures of cortical neurons. J Neurosci 21:9101-9111.
53. Mao R, Wang X, Spitznagel EL, Jr., Frelin LP, Ting JC, Ding H, Kim JW, Ruczinski I, Downey TJ, Pevsner J. 2005. Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart. Genome Biol 6:R107.
54. Marmigere F, Montelius A, Wegner M, Groner Y, Reichardt LF, Ernfors P. 2006. The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons. Nat Neurosci 9:180-187.
55. McCormick MK, Schinzel A, Petersen MB, Stetten G, Driscoll DJ, Cantu ES, Tranebjaerg L, Mikkelsen M, Watkins PC, Antonarakis SE. 1989. Molecular genetic approach to the characterization of the "Down syndrome region" of chromosome 21. Genomics 5:325-331.
56. Mertens AE, Roovers RC, Collard JG. 2003. Regulation of Tiam1-Rac signalling. FEBS Lett 546:11-16.
57. Nikolaienko O, Nguyen C, Crinc LS, Cios KJ, Gardiner K. 2005. Human chromosome 21/Down syndrome gene function and pathway database. Gene 364:90-98.
58. O'Doherty A, Ruf S, Mulligan C, Hildreth V, Errington ML, Cooke S, Sesay A, Modino S, Vanes L, Hernandez D, Linehan JM, Sharpe PT, Brandner S, Bliss TV, Henderson DJ, Nizetic D, Tybulewicz VL, Fisher EM. 2005. An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309:2033-2037.
59. Olson LE, Roper RJ, Baxter LL, Carlson EJ, Epstein CJ, Reeves RH. 2004. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev Dyn 230:581-589.
60. Pennington BF, Moon J, Edgin J, Stedron J, Nadel L. 2003. The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev 74:75-93.
61. Potier MC, Rivals I, Mercier G, Ettwiller L, Moldrich RX, Laffaire J, Personnaz L, Rossier J, Dauphinot L. 2006. Transcriptional disruptions in Down syndrome: a case study in the Ts1Cje mouse cerebellum during post-natal development. J Neurochem.
62. Pucharcos C, Fuentes JJ, Casas C, de la Luna S, Alcantara S, Arbones ML, Soriano E, Estivill X, Pritchard M. 1999. Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome. Eur J Hum Genet 7:704-712.
63. Ramakrishna N, Meeker C, Li S, Jenkins EC, Currie JR, Flory M, Lee B, Liu MS, Miller DL. 2005. Polymerase chain reaction method to identify Down syndrome model segmentally trisomic mice. Anal Biochem 340: 213-219.
64. Reeves RH, Baxter LL, Richtsmeier JT. 2001. Too much of a good thing: mechanisms of gene action in Down syndrome. Trends Genet 17:83-88.
65. Reeves RH, Irving NG, Moran TH, Wohn A, Kitt C, Sisodia SS, Schmidt C, Bronson RT, Davisson MT. 1995. A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11:177-184.
66. Roizen NJ, Patterson D. 2003. Down's syndrome. Lancet 361:1281-1289.
67. Sago H, Carlson EJ, Smith DJ, Kilbridge J, Rubin EM, Mobley WC, Epstein CJ, Huang TT. 1998. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc Natl Acad Sci U S A 95:6256-6261.
68. Sago H, Carlson EJ, Smith DJ, Rubin EM, Crnic LS, Huang TT, Epstein CJ. 2000. Genetic dissection of region associated with behavioral abnormalities in mouse models for Down syndrome. Pediatr Res 48:606-613.
69. Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC. 2006. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51:29-42.
70. Saran NG, Pletcher MT, Natale JE, Cheng Y, Reeves RH. 2003. Global disruption of the cerebellar transcriptome in a Down syndrome mouse model. Hum Mol Genet 12:2013-2019.
71. Seo H, Isacson O. 2005. Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice. Exp Neurol 193:469-480.
72. Shapiro BL. 1989. The pathogenesis of aneuploid phenotypes: the fallacy of explanatory reductionism. Am J Med Genet 33:146-151.
73. Shepherd GM. 1996. The dendritic spine: a multifunctional integrative unit. J Neurophysiol 75:2197-2210.
74. Siarey RJ, Stoll J, Rapoport SI, Galdzicki Z. 1997. Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down syndrome. Neuropharmacology 36:1549-1554.
75. Siarey RJ, Carlson EJ, Epstein CJ, Balbo A, Rapoport SI, Galdzicki Z. 1999. Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome. Neuropharmacology 38:1917-1920.
76. Siarey RJ, Villar AJ, Epstein CJ, Galdzicki Z. 2005. Abnormal synaptic plasticity in the Ts1Cje segmental trisomy 16 mouse model of Down syndrome. Neuropharmacology 49:122-128.
77. Stamnes M. 2002. Regulating the actin cytoskeleton during vesicular transport. Curr Opin Cell Biol 14:428-433.
78. Toyoda A, Noguchi H, Taylor TD, Ito T, Pletcher MT, Sakaki Y, Reeves RH, Hattori M. 2002. Comparative genomic sequence analysis of the human chromosome 21 Down syndrome critical region. Genome Res 12:1323-1332.
79. Uecker A, Obrzut JE. 1993. Hemisphere and gender differences in mental rotation. Brain Cogn 22:42-50.
80. Vialard F, Toyama K, Vernoux S, Carlson EJ, Epstein CJ, Sinet PM, Rahmani Z. 2000. Overexpression of mSim2 gene in the zona limitans of the diencephalon of segmental trisomy 16 Ts1Cje fetuses, a mouse model for trisomy 21: a novel whole-mount based RNA hybridization study. Brain Res Dev Brain Res 121:73-78.
81. Villar AJ, Belichenko PV, Gillespie AM, Kozy HM, Mobley WC, Epstein CJ. 2005. Identification and characterization of a new Down syndrome model, Ts[Rb(12.1716)]2Cje, resulting from a spontaneous Robertsonian fusion between T(171)65Dn and mouse chromosome 12. Mamm Genome 16:79-90.
82. Williams CA, Frias JL, McCormick MK, Antonarakis SE, Cantu ES. 1990. Clinical, cytogenetic, and molecular evaluation of a patient with partial trisomy 21 (21q11-q22) lacking the classical Down syndrome phenotype. Am J Med Genet Suppl 7:110-114.
83. Yates CM, Simpson J, Gordon A, Maloney AF, Allison Y, Ritchie IM, Urquhart A. 1983. Catecholamines and cholinergic enzymes in presenile and senile Alzheimer-type dementia and Down's syndrome. Brain Res 280:119-126.
84. Zhang H, Macara IG. 2006. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nat Cell Biol 8:227-237.