Skip to main content
SpringerLink
Log in

Aged wild-type littermates and APPswe+PS1/ΔE9 mice present similar deficits in associative learning and spatial memory independent of amyloid load

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

APPswe+PS1/ΔE9 transgenic (Tg) mice with Aβ plaque formation in neocortex and hippocampus were evaluated in tests measuring exploratory activity, anxiety, and memory ability using open field test (OFT), Y-maze, contextual fear conditioning (CFC), and Morris water maze (MWM). Wild type (WT) and Tg mice over eight months old showed same locomotion activity and anxiety level in novel stimulation, open field, and Y-maze contexts. In other experiments that measured associative memory and spatial memory in Tg mice and their littermates, the subjects also presented similar deficiencies in memory acquisition. These two aged groups showed abnormal freezing level variance especially in CFC test. In comparison to that in non-transgenic 8-week-old mice group, the acquisition of spatial memory in MWM task was impaired in aged WT and bigenic Tg mice. Taken together, aged wild-type littermates and Tg mice present similar deficits in associative learning and spatial memory independent of amyloid plaques.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arendash GW, King DL, Gordon MN, Morgan D, Hatcher JM, Hope CE and Diamond DM (2001) Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes. Brain Res. 891: 42–53.

    Article  CAS  PubMed  Google Scholar 

  • Belzung C and Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav. Brain Res. 125: 141–149.

    Article  CAS  PubMed  Google Scholar 

  • Bertholet JY and Crusio WE (1991) Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains. Behav. Brain Res. 43: 197–202.

    Article  CAS  PubMed  Google Scholar 

  • Brandeis R, Brandys Y and Yehuda S (1989) The use of the Morris Water Maze in the study of memory and learning. Int. J. Neurosci. 48: 29–69.

    Article  CAS  PubMed  Google Scholar 

  • Buckner RL (2004) Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44: 195–208.

    Article  CAS  PubMed  Google Scholar 

  • Buttini M, Yu GQ, Shockley K, Huang Y, Jones B, Masliah E, Mallory M, Yeo T, Longo FM and Mucke L (2002) Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation. J. Neurosci. 22: 10539–10548.

    CAS  PubMed  Google Scholar 

  • Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, Shirao T, Aoki C and Huerta PT (2006) AMPA receptor downscaling at the onset of Alzheimer’ disease pathology in double knockin mice. Proc. Natl. Acad. Sci. USA 103: 3410–3415.

    Article  CAS  PubMed  Google Scholar 

  • Dickey CA, Loring JF, Montgomery J, Gordon MN, Eastman PS and Morgan D (2003) Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23: 5219–5226.

    CAS  PubMed  Google Scholar 

  • Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, et al. (1996) Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383: 710–713.

    Article  CAS  PubMed  Google Scholar 

  • Gilpin H, Whitcomb D and Cho K (2008) Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects. Mol. Brain 1: 4.

    Article  PubMed  Google Scholar 

  • Grauer E and Kapon Y (1993) Wistar-Kyoto rats in the Morris water maze: impaired working memory and hyper-reactivity to stress. Behav. Brain Res. 59: 147–151.

    Article  CAS  PubMed  Google Scholar 

  • Gruart A, Lopez-Ramos JC, Munoz MD and Delgado-Garcia JM (2008) Aged wild-type and APP, PS1, and APP + PS1 mice present similar deficits in associative learning and synaptic plasticity independent of amyloid load. Neurobiol. Dis. 30: 439–450.

    Article  CAS  PubMed  Google Scholar 

  • Haxby JV, Raffaele K, Gillette J, Schapiro MB and Rapoport SI (1992) Individual trajectories of cognitive decline in patients with dementia of the Alzheimer type. J. Clin. Exp. Neuropsychol. 14: 575–592.

    Article  CAS  PubMed  Google Scholar 

  • Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, Saad I, Mueller R, Morgan D, et al. (1998) Accelerated Alzheimer-type phenotype in transgenic micecarrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med. 4: 97–100.

    Article  CAS  PubMed  Google Scholar 

  • Holcomb LA, Gordon MN, Jantzen P, Hsiao K, Duff K and Morgan D (1999) Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav. Genet. 29: 177–185.

    Article  CAS  PubMed  Google Scholar 

  • Hollingworth P, Hamshere ML, Moskvina V, Dowzell K, Moore PJ, Foy C, Archer N, Lynch A, Lovestone S, Brayne C, et al. (2006) Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer’ disease. J. Am. Geriatr. Soc. 54: 1348–1354.

    Article  PubMed  Google Scholar 

  • Holscher C (1999) Stress impairs performance in spatial water maze learning tasks. Behav. Brain Res. 100: 225–235.

    Article  CAS  PubMed  Google Scholar 

  • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F and Cole G (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274: 99–102.

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, et al. (2006) Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer’ disease. Proc. Natl. Acad. Sci. USA 103: 5161–5166.

    Article  CAS  PubMed  Google Scholar 

  • Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, et al. (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13: 159–170.

    Article  CAS  PubMed  Google Scholar 

  • Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR and Savonenko AV (2005) Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’ disease. J. Neurosci. 25: 5217–5224.

    Article  CAS  PubMed  Google Scholar 

  • Kelly PH, Bondolfi L, Hunziker D, Schlecht HP, Carver K, Maguire E, Abramowski D, Wiederhold KH, Sturchler-Pierrat C, Jucker M, et al. (2003) Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol. Aging 24: 365–378.

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Lee S, Park K, Hong I, Song B, Son G, Park H, Kim WR, Park E, Choe HK, et al. (2007) Amygdala depotentiation and fear extinction. Proc. Natl. Acad. Sci. USA 104: 20955–20960.

    Article  CAS  PubMed  Google Scholar 

  • Kim JJ and Fanselow MS (1992) Modality-specific retrograde amnesia of fear. Science 256: 675–677.

    Article  CAS  PubMed  Google Scholar 

  • King DL and Arendash GW (2002) Behavioral characterization of the Tg2576 transgenic model of Alzheimer’ disease through 19 months. Physiol. Behav. 75: 627–642.

    Article  CAS  PubMed  Google Scholar 

  • Lalonde R, Kim HD and Fukuchi K (2004) Exploratory activity, anxiety, and motor coordination in bigenic APPswe+PS1/DeltaE9 mice. Neurosci. Lett. 369: 156–161.

    Article  CAS  PubMed  Google Scholar 

  • Lalonde R, Lewis TL, Strazielle C, Kim H and Fukuchi K (2003) Transgenic mice expressing the betaAPP695SWE mutation: effects on exploratory activity, anxiety, and motor coordination. Brain Res. 977: 38–45.

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Chang DJ, Lee YS, Chang KA, Kim H, Yoon JS, Lee S, Suh YH and Kaang BK (2003) Beta-amyloid peptide binding protein does not couple to G protein in a heterologous Xenopus expression system. J. Neurosci. Res. 73: 255–259.

    Article  CAS  PubMed  Google Scholar 

  • Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K and et al. (1995) Candidate gene for the chromosome 1 familial Alzheimer’ disease locus. Science 269: 973–977.

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Orozco IJ, Planel E, Wen Y, Bretteville A, Krishnamurthy P, Wang L, Herman M, Figueroa H, Yu WH, et al. (2008) A transgenic rat that develops Alzheimer’ disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurobiol. Dis. 31: 46–57.

    Article  CAS  PubMed  Google Scholar 

  • Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47–60.

    Article  CAS  PubMed  Google Scholar 

  • Nilsson LN, Bales KR, DiCarlo G, Gordon MN, Morgan D, Paul SM and Potter H (2001) Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer’ disease. J. Neurosci. 21: 1444–1451.

    CAS  PubMed  Google Scholar 

  • Prut L and Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur. J. Pharmacol. 463: 3–33.

    Article  CAS  PubMed  Google Scholar 

  • Rapp PR and Amaral DG (1992) Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci 15: 340–345.

    Article  CAS  PubMed  Google Scholar 

  • Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ and Mucke L (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’ disease mouse model. Science 316: 750–754.

    Article  CAS  PubMed  Google Scholar 

  • Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, et al. (1995) Familial Alzheimer’ disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’ disease type 3 gene. Nature 376: 775–778.

    Article  CAS  PubMed  Google Scholar 

  • Sarter M, Bodewitz G and Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology (Berl) 94: 491–495.

    Article  CAS  Google Scholar 

  • Saura CA, Chen G, Malkani S, Choi SY, Takahashi RH, Zhang D, Gouras GK, Kirkwood A, Morris RG and Shen J (2005) Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J. Neurosci. 25: 6755–6764.

    Article  CAS  PubMed  Google Scholar 

  • Savonenko AV, Xu GM, Price DL, Borchelt DR and Markowska AL (2003) Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APP SWE. Neurobiol. Dis. 12: 194–211.

    Article  CAS  PubMed  Google Scholar 

  • Terry RD and Katzman R (1983) Senile dementia of the Alzheimer type. Ann. Neurol. 14: 497–506.

    Article  CAS  PubMed  Google Scholar 

  • Wang SH, Teixeira CM, Wheeler AL and Frankland PW (2009) The precision of remote context memories does not require the hippocampus. Nat. Neurosci. 12: 253–255.

    Article  PubMed  Google Scholar 

  • Wenk GL (2004) Assessment of spatial memory using the radial arm maze and Morris water maze. Curr. Protoc. Neurosci. Chapter 8: Unit 8 5A.

  • Whitehouse PJ, Price DL, Clark AW, Coyle JT and DeLong MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 10: 122–126.

    Article  CAS  PubMed  Google Scholar 

  • Wong TP, Debeir T, Duff K and Cuello AC (1999) Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J. Neurosci. 19: 2706–2716.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Creative Research Initiative Center for Memory, Departments of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-747, Korea

    Soo-Won Park, Hyoung-Gon Ko, Nuribalhae Lee, Hye-Ryeon Lee, Young-Soo Rim, Hyoung Kim & Bong-Kiun Kaang

  2. Department of Anatomy, School of Medicine, Kyungpook National University, 101 Donin-dong 2 Ga, Jung-gu, Daegu, 700-422, Korea

    Kyung-Min Lee

  3. Departments of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-747, Korea

    Bong-Kiun Kaang

Authors
  1. Soo-Won Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyoung-Gon Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nuribalhae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hye-Ryeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young-Soo Rim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyung-Min Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bong-Kiun Kaang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bong-Kiun Kaang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, SW., Ko, HG., Lee, N. et al. Aged wild-type littermates and APPswe+PS1/ΔE9 mice present similar deficits in associative learning and spatial memory independent of amyloid load. Genes Genom 32, 63–70 (2010). https://doi.org/10.1007/s13258-010-0833-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-010-0833-8

Keywords

Search

Navigation