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volume 48 issue 4 (august 2014) : 389-394,   Doi: 10.5958/0976–0555.2014.00462.2

BEHAVIORAL AND PATHOLOGICAL CHANGES IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASE

D
Dong Xian-hui
G
Gao Wei-juan1
K
Kong Wei-na1
C
Chai Xi-qing1*
1Department of Neurology, the first Hospital of Hebei Medical University, Shijiazhuang-050 000, China
Cite article:- Xian-hui Dong, Wei-juan1 Gao, Wei-na1 Kong, Xi-qing1* Chai (2025). BEHAVIORAL AND PATHOLOGICAL CHANGES IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASE. Indian Journal of Animal Research. 48(4): 389-394. doi: 10.5958/0976–0555.2014.00462.2.

ABSTRACT

Alzheimer’s disease (AD), a neurodegenerative brain disorder, is the most common cause of dementia, characterized by amyloid-b plaque accumulation, intracellular tangles and neuronal loss in selective brain regions. The frontal cortex, important for executive functioning, is one of the regions affected. In this communication, it has been investigated that learning and memory function and pathological changes of APPswe/PS1DE9 (APP/PS1) double transgenic mouse. Ten male APP/PS1 double transgenic mice and 10 male C57BL/6J mice were used in this study. The learning and memory functions were studied by Morris water maze, the pathological changes in brain tissue by modified Bielschowsky and Nissl’s staining and the distribution of Aâ plaques in the APP/PS1 mouse brain by immunohistochemistry using avidin-biotinylated complex staining. We found that the APP/PS1 mice provided novel insights into the regional selective vulnerability of the frontal cortex to Alzheimer’s disease and therefore these mice may prove as useful animal models for understanding the pathogenesis of Alzheimer’s disease in people.

REFERENCES

  1. Armstrong R.A. (2013). What causes alzheimer’s disease. Folia Neuropathol, 51(3):169-188.
  2. Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. (2012). Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res, 9(5):563-573.
  3. Cheng D, Low JK, Logge W, Garner B3, Karl T4. (2014). Novel behavioural characteristics of female APPSwe/PS1DE9 double transgenic mice. Behav Brain Res, 260(3):111-118.
  4. De Caluwé J, Dupont G. (2013). The progression towards Alzheimer’s disease described as a bistable switch arising from the positive loop between amyloids and Ca(2+). J Theor Biol, 331(1):12-18.
  5. Delacourte A, Sergeant N, Champain D, Wattez A, Maurage CA, Lebert F, Pasquier F, David JP. (2002). Nonoverlapping but synergetic tau and amyloid precursor protein pathologies in sporadic Alzheimer’s disease. Neurology, 59: 398-407.
  6. Depboylu C, Lohmüller F, Du Y, Riemenschneider M, Kurz A, Gasser T, Müller U, Dodel RC. (2006). Alpha2-macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer’s disease. Neurosci Lett, 400(3):187-190.
  7. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer’s Disease International. (2005). Global prevalence of dementia: a Delphi consensus study. Alzheimer’s Disease. International Lancet, 366(9503):2112-2117.
  8. Ferretti MT, Partridge V, Leon WC, Canneva F, Allard S, Arvanitis DN, Vercauteren F, Houle D, Ducatenzeiler A, Klein WL, Glabe CG, Szyf M,Cuello AC. (2011). Transgenic mice as a model of pre-clinical Alzheimer’s disease. Curr Alzheimer Res, 8(1):4-23.
  9. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 349: 704-706.
  10. Hall AM, Roberson ED. (2012). Mouse models of Alzheimer’s disease. Brain Res Bull, 88(1):3-12.
  11. Hollingworth P, Harold D, Sims R, et al. (2011). Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet, 43(5):429-435.
  12. Jun G, Naj AC, Beecham GW, et al. (2010). Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol, 67(12):1473-1484.
  13. Koldamova R, Schug J, Lefterova M, Cronican AA, Fitz NF, Davenport FA, Carter A, Castranio EL4, Lefterov I5. (2014). Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration. Neurobiol Dis, 63(3):107-114.
  14. Li J, Wang YJ, Zhang M, Fang CQ, Zhou HD. (2011). Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer’s disease. Life Sci, 89(3-4):86-92.
  15. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Ramsey K, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette CM, Schmechel D,Reiman EM, Rogers J, Stephan DA. (2010). Neuronal gene expression in non-    demented individuals with intermediate Alzheimer’s Diseaseneuropathology. Neurobiol Aging, 31(4):549-566.
  16. Morris R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods, 11(1):47-60.
  17. Nobakht M, Hoseini SM, Mortazavi P, Sohrabi I, Esmailzade B, Rahbar Rooshandel N, Omidzahir S. (2011). Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer’s disease. Iran Biomed J, 15(1-    2):51-58.
  18. Nojima J, Maeda A, Aoki S, Suo S, Yanagihara D, Watanabe Y, Yoshida T, Ishiura S. (2011). Effect of rice-expressed amyloid â in the Tg2576 Alzheimer’s disease transgenic mouse model. Vaccine, 29(37):6252-6258.
  19. Naj AC, Jun G, Beecham GW, et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet, 43(5):436-441.
  20. Quiroz YT, Stern CE, Reiman EM, Brickhouse M, Ruiz A, Sperling RA, Lopera F, Dickerson BC. (2013). Cortical atrophy in presymptomatic Alzheimer’s disease presenilin 1 mutation carriers. J Neurol Neurosurg Psychiatry, 84(5):556-561.
  21. Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, Ayutyanont N, Keppler J, Reeder SA, Langbaum JB, Alexander GE, Klunk WE, Mathis CA,Price JC, Aizenstein HJ, DeKosky ST, Caselli RJ. (2009). Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA, 106(16):6820-6825.
  22. Steiner H, Capell A, Leimer U, Haass C. (1999). Genes and mechanisms involved in beta-amyloid generation and Alzheimer’s disease. Eur Arch Psych and Clin Neurol, 249: 266-270.
  23. Wang D, Gao K, Li X, Shen X, Zhang X, Ma C, Qin C, Zhang L. (2012). Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficitsin a mouse model of Alzheimer’s disease. Pharmacol Biochem Behav, 102(1):13-20.
  24. Yue Yang, Christine Shiao, Jake Frederick Hemingway. (2013). Suppressed Retinal Degeneration in Aged Wild Type and APPswe/PS1ÄE9 Mice by Bone Marrow Transplantation. PLoS One, 8(6): e64246.
  25. Zhang J, Zhen YF, Pu-Bu-Ci-Ren, Song LG, Kong WN, Shao TM, Li X, Chai XQ. (2013). Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stressand inflammatory mediators in rat hippocampus. Behav Brain Res, 244:70-81.
  26. Zong Y, Wang H, Dong W, Quan X, Zhu H, Xu Y, Huang L, Ma C, Qin C. (2011). miR-29c regulates BACE1 protein expression. Brain Res, 1395:108-115.
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Indian Journal of Animal Research
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    volume 48 issue 4 (august 2014) : 389-394,   Doi: 10.5958/0976–0555.2014.00462.2

    BEHAVIORAL AND PATHOLOGICAL CHANGES IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASE

    D
    Dong Xian-hui
    G
    Gao Wei-juan1
    K
    Kong Wei-na1
    C
    Chai Xi-qing1*
    1Department of Neurology, the first Hospital of Hebei Medical University, Shijiazhuang-050 000, China
    Cite article:- Xian-hui Dong, Wei-juan1 Gao, Wei-na1 Kong, Xi-qing1* Chai (2025). BEHAVIORAL AND PATHOLOGICAL CHANGES IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASE. Indian Journal of Animal Research. 48(4): 389-394. doi: 10.5958/0976–0555.2014.00462.2.

    ABSTRACT

    Alzheimer’s disease (AD), a neurodegenerative brain disorder, is the most common cause of dementia, characterized by amyloid-b plaque accumulation, intracellular tangles and neuronal loss in selective brain regions. The frontal cortex, important for executive functioning, is one of the regions affected. In this communication, it has been investigated that learning and memory function and pathological changes of APPswe/PS1DE9 (APP/PS1) double transgenic mouse. Ten male APP/PS1 double transgenic mice and 10 male C57BL/6J mice were used in this study. The learning and memory functions were studied by Morris water maze, the pathological changes in brain tissue by modified Bielschowsky and Nissl’s staining and the distribution of Aâ plaques in the APP/PS1 mouse brain by immunohistochemistry using avidin-biotinylated complex staining. We found that the APP/PS1 mice provided novel insights into the regional selective vulnerability of the frontal cortex to Alzheimer’s disease and therefore these mice may prove as useful animal models for understanding the pathogenesis of Alzheimer’s disease in people.

    REFERENCES

    1. Armstrong R.A. (2013). What causes alzheimer’s disease. Folia Neuropathol, 51(3):169-188.
    2. Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. (2012). Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res, 9(5):563-573.
    3. Cheng D, Low JK, Logge W, Garner B3, Karl T4. (2014). Novel behavioural characteristics of female APPSwe/PS1DE9 double transgenic mice. Behav Brain Res, 260(3):111-118.
    4. De Caluwé J, Dupont G. (2013). The progression towards Alzheimer’s disease described as a bistable switch arising from the positive loop between amyloids and Ca(2+). J Theor Biol, 331(1):12-18.
    5. Delacourte A, Sergeant N, Champain D, Wattez A, Maurage CA, Lebert F, Pasquier F, David JP. (2002). Nonoverlapping but synergetic tau and amyloid precursor protein pathologies in sporadic Alzheimer’s disease. Neurology, 59: 398-407.
    6. Depboylu C, Lohmüller F, Du Y, Riemenschneider M, Kurz A, Gasser T, Müller U, Dodel RC. (2006). Alpha2-macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer’s disease. Neurosci Lett, 400(3):187-190.
    7. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer’s Disease International. (2005). Global prevalence of dementia: a Delphi consensus study. Alzheimer’s Disease. International Lancet, 366(9503):2112-2117.
    8. Ferretti MT, Partridge V, Leon WC, Canneva F, Allard S, Arvanitis DN, Vercauteren F, Houle D, Ducatenzeiler A, Klein WL, Glabe CG, Szyf M,Cuello AC. (2011). Transgenic mice as a model of pre-clinical Alzheimer’s disease. Curr Alzheimer Res, 8(1):4-23.
    9. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 349: 704-706.
    10. Hall AM, Roberson ED. (2012). Mouse models of Alzheimer’s disease. Brain Res Bull, 88(1):3-12.
    11. Hollingworth P, Harold D, Sims R, et al. (2011). Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet, 43(5):429-435.
    12. Jun G, Naj AC, Beecham GW, et al. (2010). Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol, 67(12):1473-1484.
    13. Koldamova R, Schug J, Lefterova M, Cronican AA, Fitz NF, Davenport FA, Carter A, Castranio EL4, Lefterov I5. (2014). Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration. Neurobiol Dis, 63(3):107-114.
    14. Li J, Wang YJ, Zhang M, Fang CQ, Zhou HD. (2011). Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer’s disease. Life Sci, 89(3-4):86-92.
    15. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Ramsey K, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette CM, Schmechel D,Reiman EM, Rogers J, Stephan DA. (2010). Neuronal gene expression in non-    demented individuals with intermediate Alzheimer’s Diseaseneuropathology. Neurobiol Aging, 31(4):549-566.
    16. Morris R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods, 11(1):47-60.
    17. Nobakht M, Hoseini SM, Mortazavi P, Sohrabi I, Esmailzade B, Rahbar Rooshandel N, Omidzahir S. (2011). Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer’s disease. Iran Biomed J, 15(1-    2):51-58.
    18. Nojima J, Maeda A, Aoki S, Suo S, Yanagihara D, Watanabe Y, Yoshida T, Ishiura S. (2011). Effect of rice-expressed amyloid â in the Tg2576 Alzheimer’s disease transgenic mouse model. Vaccine, 29(37):6252-6258.
    19. Naj AC, Jun G, Beecham GW, et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet, 43(5):436-441.
    20. Quiroz YT, Stern CE, Reiman EM, Brickhouse M, Ruiz A, Sperling RA, Lopera F, Dickerson BC. (2013). Cortical atrophy in presymptomatic Alzheimer’s disease presenilin 1 mutation carriers. J Neurol Neurosurg Psychiatry, 84(5):556-561.
    21. Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, Ayutyanont N, Keppler J, Reeder SA, Langbaum JB, Alexander GE, Klunk WE, Mathis CA,Price JC, Aizenstein HJ, DeKosky ST, Caselli RJ. (2009). Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA, 106(16):6820-6825.
    22. Steiner H, Capell A, Leimer U, Haass C. (1999). Genes and mechanisms involved in beta-amyloid generation and Alzheimer’s disease. Eur Arch Psych and Clin Neurol, 249: 266-270.
    23. Wang D, Gao K, Li X, Shen X, Zhang X, Ma C, Qin C, Zhang L. (2012). Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficitsin a mouse model of Alzheimer’s disease. Pharmacol Biochem Behav, 102(1):13-20.
    24. Yue Yang, Christine Shiao, Jake Frederick Hemingway. (2013). Suppressed Retinal Degeneration in Aged Wild Type and APPswe/PS1ÄE9 Mice by Bone Marrow Transplantation. PLoS One, 8(6): e64246.
    25. Zhang J, Zhen YF, Pu-Bu-Ci-Ren, Song LG, Kong WN, Shao TM, Li X, Chai XQ. (2013). Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stressand inflammatory mediators in rat hippocampus. Behav Brain Res, 244:70-81.
    26. Zong Y, Wang H, Dong W, Quan X, Zhu H, Xu Y, Huang L, Ma C, Qin C. (2011). miR-29c regulates BACE1 protein expression. Brain Res, 1395:108-115.
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