Neurobiology of Aging
Volume 30, Issue 8 , Pages 1227-1237 , August 2009

Excitatory synaptic transmission is depressed in cultured hippocampal neurons of APP/PS1 mice

  • Christina Priller

      Affiliations

    • Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, Feodor-Lynen-Strasse 23, 81377 München, Germany
    • ,
  • Gerda Mitteregger

      Affiliations

    • Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, Feodor-Lynen-Strasse 23, 81377 München, Germany
    • ,
  • Sandra Paluch

      Affiliations

    • Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, Feodor-Lynen-Strasse 23, 81377 München, Germany
    • ,
  • Neville Vassallo

      Affiliations

    • Department of Physiology and Biochemistry, University of Malta, Msida MS06, Malta, Germany
    • ,
  • Matthias Staufenbiel

      Affiliations

    • Novartis Institutes for Biomedical Research, Neuroscience Research, 4002 Basel, Switzerland
    • ,
  • Hans A. Kretzschmar

      Affiliations

    • Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, Feodor-Lynen-Strasse 23, 81377 München, Germany
    • ,
  • Mathias Jucker

      Affiliations

    • Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, Otfried-Muller Strasse 27, D-72076 Tübingen, Germany
    • ,
  • Jochen Herms

      Affiliations

    • Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, Feodor-Lynen-Strasse 23, 81377 München, Germany
    • Corresponding Author InformationCorresponding author.

Received 8 August 2007 ,Revised 18 October 2007 ,Accepted 25 October 2007.

References 

  1. Almeida CG, Tampellini D, Takahashi RH, Greengard P, Lin MT, Snyder EM, et al. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol. Dis. 2005;20:187–198
  2. Augustin I, Rosenmund C, Sudhof TC, Brose N. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature. 1999;400:457–461
  3. Bekkers JM, Stevens CF. Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture. Proc. Natl. Acad. Sci. U.S.A. 1991;88:7834–7838
  4. Bentahir M, Nyabi O, Verhamme J, Tolia A, Horre K, Wiltfang J, et al. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J. Neurochem. 2006;96:732–742
  5. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, et al. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997;19:939–945
  6. Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, et al. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron. 1996;17:1005–1013
  7. Cai XD, Golde TE, Younkin SG. Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science. 1993;259:514–516
  8. Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, et al. AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice. Proc. Natl. Acad. Sci. U.S.A. 2006;103:3410–3415
  9. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, et al. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat. Neurosci. 1999;2:271–276
  10. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, et al. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature. 1992;360:672–674
  11. Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 1997;3:67–72
  12. Coleman P, Federoff H, Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology. 2004;63:1155–1162
  13. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999;398:518–522
  14. Demuro A, Mina E, Kayed R, Milton SC, Parker I, Glabe CG. Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. J. Biol. Chem. 2005;280:17294–17300
  15. Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol. Aging. 1995;16:285–298
  16. Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD. Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: in vitro and in vivo mechanisms related to Alzheimer's disease. J. Neurosci. 2001;21:4125–4133
  17. Fink CC, Bayer KU, Myers JW, Ferrell JE, Schulman H, Meyer T. Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII. Neuron. 2003;39:283–297
  18. Fitzjohn SM, Morton RA, Kuenzi F, Rosahl TW, Shearman M, Lewis H, et al. Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein. J. Neurosci. 2001;21:4691–4698
  19. Flood DG, Coleman PD. Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease. Prog. Brain Res. 1990;83:435–443
  20. Gomez-Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 1996;16:4491–4500
  21. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. U.S.A. 1986;83:4913–4917
  22. Hamid R, Kilger E, Willem M, Vassallo N, Kostka M, Bornhovd C, et al. Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content. J. Neurochem. 2007;102:1264–1275
  23. Hartmann T. Intracellular biology of Alzheimer's disease amyloid beta peptide. Eur. Arch. Psychiatry Clin. Neurosci. 1999;249:291–298
  24. Herms J, Schneider I, Dewachter I, Caluwaerts N, Kretzschmar H, Van Leuven F. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J. Biol. Chem. 2003;278:2484–2489
  25. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med. 1998;4:97–100
  26. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. U.S.A. 1999;96:3228–3233
  27. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996;274:99–102
  28. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron. 2006;52:831–843
  29. Ihara Y, Nukina N, Miura R, Ogawara M. Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer's disease. J. Biochem. (Tokyo). 1986;99:1807–1810
  30. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, et al. APP processing and synaptic function. Neuron. 2003;37:925–937
  31. LaFerla FM. Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat. Rev. Neurosci. 2002;3:862–872
  32. Larson J, Lynch G, Games D, Seubert P. Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice. Brain Res. 1999;840:23–35
  33. Lee HG, Moreira PI, Zhu X, Smith MA, Perry G. Staying connected: synapses in Alzheimer disease. Am. J. Pathol. 2004;165:1461–1464
  34. Leissring MA, Murphy MP, Mead TR, Akbari Y, Sugarman MC, Jannatipour M, et al. A physiologic signaling role for the gamma-secretase-derived intracellular fragment of APP. Proc. Natl. Acad. Sci. U.S.A. 2002;99:4697–4702
  35. Leissring MA, Paul BA, Parker I, Cotman CW, LaFerla FM. Alzheimer's presenilin-1 mutation potentiates inositol 1,4,5-trisphosphate-mediated calcium signaling in Xenopus oocytes. J. Neurochem. 1999;72:1061–1068
  36. Moechars D, Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, et al. Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J. Biol. Chem. 1999;274:6483–6492
  37. Moehlmann T, Winkler E, Xia X, Edbauer D, Murrell J, Capell A, et al. Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc. Natl. Acad. Sci. U.S.A. 2002;99:8025–8030
  38. Oddo S, Caccamo A, Smith IF, Green KN, LaFerla FM. A dynamic relationship between intracellular and extracellular pools of Abeta. Am. J. Pathol. 2006;168:184–194
  39. Priller C, Dewachter I, Vassallo N, Paluch S, Pace C, Kretzschmar HA, et al. Mutant presenilin 1 alters synaptic transmission in cultured hippocampal neurons. J. Biol. Chem. 2007;282:1119–1127
  40. Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D, Stoltze L, et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep. 2006;7:940–946
  41. Reim K, Mansour M, Varoqueaux F, McMahon HT, Sudhof TC, Brose N, et al. Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell. 2001;104:71–81
  42. Rosenmund C, Clements JD, Westbrook GL. Nonuniform probability of glutamate release at a hippocampal synapse. Science. 1993;262:754–757
  43. Rosenmund C, Feltz A, Westbrook GL. Calcium-dependent inactivation of synaptic NMDA-receptors in hippocampal neurons. J. Neurophysiol. 1995;73:427–430
  44. Rosenmund C, Stevens CF. Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron. 1996;16:1197–1207
  45. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron. 2004;42:23–36
  46. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat. Med. 1996;2:864–870
  47. Schneider I, Reverse D, Dewachter I, Ris L, Caluwaerts N, Kuiperi C, et al. Mutant presenilins disturb neuronal calcium homeostasis in the brain of transgenic mice, decreasing the threshold for excitotoxicity and facilitating long-term potentiation. J. Biol. Chem. 2001;276:11539–11544
  48. Selkoe DJ. Amyloid beta-protein and the genetics of Alzheimer's disease. J. Biol. Chem. 1996;271:18295–18298
  49. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298:789–791
  50. Shen J, Kelleher RJ. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc. Natl. Acad. Sci. U.S.A. 2007;104:403–409
  51. Shi S, Hayashi Y, Esteban JA, Malinow R. Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell. 2001;105:331–343
  52. Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA-receptor activation. Science. 1999;284:1811–1816
  53. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, et al. Regulation of NMDA-receptor trafficking by amyloid-beta. Nat. Neurosci. 2005;8:1051–1058
  54. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. U.S.A. 1997;94:13287–13292
  55. Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, et al. Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain. J. Neurosci. 2004;24:3592–3599
  56. Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, et al. Intraneuronal Alzheimer abeta42 accumulates in multi-vesicular bodies and is associated with synaptic pathology. Am. J. Pathol. 2002;161:1869–1879
  57. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 1991;30:572–580
  58. Ting JT, Kelley BG, Lambert TJ, Cook DG, Sullivan JM. Amyloid precursor protein overexpression depresses excitatory transmission through both pre-synaptic and post-synaptic mechanisms. Proc. Natl. Acad. Sci. U.S.A. 2007;104:353–358
  59. Tseng BP, Green KN, Chan JL, Blurton-Jones M, LaFerla FM. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol. Aging. 2007;
  60. Vetrivel KS, Cheng H, Kim SH, Chen Y, Barnes NY, Parent AT, et al. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J. Biol. Chem. 2005;280:25892–25900
  61. Wang HY, Lee DH, Davis CB, Shank RP. Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors. J. Neurochem. 2000;75:1155–1161
  62. Williams EJ, Doherty P, Turner G, Reid RA, Hemperly JJ, Walsh FS. Calcium influx into neurons can solely account for cell contact-dependent neurite outgrowth stimulated by transfected L1. J. Cell Biol. 1992;119:883–892
  63. Wilson CA, Doms RW, Lee VM. Intracellular APP processing and A beta production in Alzheimer disease. J. Neuropathol. Exp. Neurol. 1999;58:787–794
  64. Wolfe MS, Haass C. The role of presenilins in gamma-secretase activity. J. Biol. Chem. 2001;276:5413–5416
  65. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, et al. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999;402:533–537
  66. Zaman SH, Parent A, Laskey A, Lee MK, Borchelt DR, Sisodia SS, et al. Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine. Neurobiol. Dis. 2000;7:54–63

PII: S0197-4580(07)00416-2

doi: 10.1016/j.neurobiolaging.2007.10.016

Neurobiology of Aging
Volume 30, Issue 8 , Pages 1227-1237 , August 2009

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