PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. TAPS Mice Accumulate Aβ Aggregates in the Striatum, Hippocampus, and Cortex as Early as 6 Months
2.2. TAPS Mice Show Phenotypic Alterations in the SHIRPA and Open Field Tests
2.3. TAPS Mice Develop Cognitive Deficits in Different Behavioral Tests
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Histology
4.3. Behavioral Tests
4.3.1. SHIRPA
4.3.2. Open Field Test
4.3.3. Novel Object Recognition Test
4.3.4. T-maze Spontaneous Alternation
4.3.5. Contextual and Cued Fear Conditioning
4.3.6. Morris Water Maze
4.4. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Prince, M.J. World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends; Alzheimer’s Disease International: London, UK, 2015. [Google Scholar]
- Wu, Y.-T.; Beiser, A.S.; Breteler, M.M.B.; Fratiglioni, L.; Helmer, C.; Hendrie, H.C.; Honda, H.; Ikram, M.A.; Langa, K.M.; Lobo, A.; et al. The changing prevalence and incidence of dementia over time—Current evidence. Nat. Rev. Neurol. 2017, 13, 327–339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nichols, E.; Szoeke, C.E.I.; Vollset, S.E.; Abbasi, N.; Abd-Allah, F.; Abdela, J.; Aichour, M.T.E.; Akinyemi, R.O.; Alahdab, F.; Asgedom, S.W.; et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019, 18, 88–106. [Google Scholar] [CrossRef] [Green Version]
- Gale, S.A.; Acar, D.; Daffner, K.R. Dementia. Am. J. Med. 2018, 131, 1161–1169. [Google Scholar] [CrossRef] [PubMed]
- Sütterlin, S.; Hoßmann, I.; Klingholz, R. Demenz-Report: Wie sich die Regionen in Deutschland, Österreich und der Schweiz auf die Alterung der Gesellschaft vorbereiten können; DEU: Berlin, Germany, 2011. [Google Scholar]
- Lannfelt, L.; Bogdanovic, N.; Appelgren, H.; Axelman, K.; Lilius, L.; Hansson, G.; Schenk, D.; Hardy, J.; Winblad, B. Amyloid precursor protein mutation causes Alzheimer’s disease in a Swedish family. Neurosci. Lett. 1994, 168, 254–256. [Google Scholar] [CrossRef]
- Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015, 16, 358–372. [Google Scholar] [CrossRef] [PubMed]
- Jankowsky, J.L.; Fadale, D.J.; Anderson, J.; Xu, G.M.; Gonzales, V.; Jenkins, N.A.; Copeland, N.G.; Lee, M.K.; Younkin, L.H.; Wagner, S.L.; et al. 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. 2004, 13, 159–170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mullan, M.; Crawford, F.; Axelman, K.; Houlden, H.; Lilius, L.; Winblad, B.; Lannfelt, L. A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N–terminus of β–amyloid. Nat. Genet. 1992, 1, 345–347. [Google Scholar] [CrossRef] [PubMed]
- Scheuner, D.; Eckman, C.; Jensen, M.; Song, X.; Citron, M.; Suzuki, N.; Bird, T.D.; Hardy, J.; Hutton, M.; Kukull, W.; 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. [Google Scholar] [CrossRef] [PubMed]
- Borchelt, D.R.; Thinakaran, G.; Eckman, C.B.; Lee, M.K.; Davenport, F.; Ratovitsky, T.; Prada, C.-M.; Kim, G.; Seekins, S.; Yager, D.; et al. Familial Alzheimer’s Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo. Neuron 1996, 17, 1005–1013. [Google Scholar] [CrossRef] [Green Version]
- Jackson, H.M.; Soto, I.; Graham, L.C.; Carter, G.W.; Howell, G.R. Clustering of transcriptional profiles identifies changes to insulin signaling as an early event in a mouse model of Alzheimer’s disease. BMC Genom. 2013, 14, 831. [Google Scholar] [CrossRef] [Green Version]
- Malm, T.M.; Iivonen, H.; Goldsteins, G.; Keksa-Goldsteine, V.; Ahtoniemi, T.; Kanninen, K.; Salminen, A.; Auriola, S.; Van Groen, T.; Tanila, H.; et al. Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting beta-amyloid burden. J. Neurosci. 2007, 27, 3712–3721. [Google Scholar] [CrossRef] [Green Version]
- Onos, K.D.; Uyar, A.; Keezer, K.J.; Jackson, H.M.; Preuss, C.; Acklin, C.J.; O’Rourke, R.; Buchanan, R.; Cossette, T.L.; Sukoff Rizzo, S.J.; et al. Enhancing face validity of mouse models of Alzheimer’s disease with natural genetic variation. PLoS Genet. 2019, 15, e1008155. [Google Scholar] [CrossRef]
- Janus, C.; Flores, A.Y.; Xu, G.; Borchelt, D.R. Behavioral abnormalities in APPSwe/PS1dE9 mouse model of AD-like pathology: Comparative analysis across multiple behavioral domains. Neurobiol. Aging 2015, 36, 2519–2532. [Google Scholar] [CrossRef] [PubMed]
- Huang, H.; Nie, S.; Cao, M.; Marshall, C.; Gao, J.; Xiao, N.; Hu, G.; Xiao, M. Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice. Age 2016, 38, 303–322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Minkeviciene, R.; Ihalainen, J.; Malm, T.; Matilainen, O.; Keksa-Goldsteine, V.; Goldsteins, G.; Iivonen, H.; Leguit, N.; Glennon, J.; Koistinaho, J.; et al. Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice. J. Neurochem. 2008, 105, 584–594. [Google Scholar] [CrossRef]
- Stenzel, J.; Rühlmann, C.; Lindner, T.; Polei, S.; Teipel, S.; Kurth, J.; Rominger, A.; Krause, B.J.; Vollmar, B.; Kuhla, A. [(18)F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9. Curr. Alzheimer Res. 2019, 16, 49–55. [Google Scholar] [CrossRef]
- Snellman, A.; López-Picón, F.R.; Rokka, J.; Salmona, M.; Forloni, G.; Scheinin, M.; Solin, O.; Rinne, J.O.; Haaparanta-Solin, M. Longitudinal Amyloid Imaging in Mouse Brain with 11C-PIB: Comparison of APP23, Tg2576, and APPswe-PS1dE9 Mouse Models of Alzheimer Disease. J. Nucl. Med. 2013, 54, 1434–1441. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maeda, J.; Ji, B.; Irie, T.; Tomiyama, T.; Maruyama, M.; Okauchi, T.; Staufenbiel, M.; Iwata, N.; Ono, M.; Saido, T.C.; et al. Longitudinal, Quantitative Assessment of Amyloid, Neuroinflammation, and Anti-Amyloid Treatment in a Living Mouse Model of Alzheimer’s Disease Enabled by Positron Emission Tomography. J. Neurosci. 2007, 27, 10957–10968. [Google Scholar] [CrossRef]
- Mori, H.; Takio, K.; Ogawara, M.; Selkoe, D.J. Mass spectrometry of purified amyloid beta protein in Alzheimer’s disease. J. Biol. Chem. 1992, 267, 17082–17086. [Google Scholar] [CrossRef]
- Harigaya, Y.; Saido, T.C.; Eckman, C.B.; Prada, C.-M.; Shoji, M.; Younkin, S.G. Amyloid β Protein Starting Pyroglutamate at Position 3 Is a Major Component of the Amyloid Deposits in the Alzheimer’s Disease Brain. Biochem. Biophys. Res. Commun. 2000, 276, 422–427. [Google Scholar] [CrossRef] [PubMed]
- Güntert, A.; Döbeli, H.; Bohrmann, B. High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits from human and PS2APP mouse brain. Neuroscience 2006, 143, 461–475. [Google Scholar] [CrossRef] [PubMed]
- Frost, J.L.; Le, K.X.; Cynis, H.; Ekpo, E.; Kleinschmidt, M.; Palmour, R.M.; Ervin, F.R.; Snigdha, S.; Cotman, C.W.; Saido, T.C.; et al. Pyroglutamate-3 Amyloid-β Deposition in the Brains of Humans, Non-Human Primates, Canines, and Alzheimer Disease–Like Transgenic Mouse Models. Am. J. Pathol. 2013, 183, 369–381. [Google Scholar] [CrossRef] [PubMed]
- Cynis, H.; Scheel, E.; Saido, T.C.; Schilling, S.; Demuth, H.-U. Amyloidogenic Processing of Amyloid Precursor Protein: Evidence of a Pivotal Role of Glutaminyl Cyclase in Generation of Pyroglutamate-Modified Amyloid-β. Biochemistry 2008, 47, 7405–7413. [Google Scholar] [CrossRef] [PubMed]
- He, W.; Barrow, C.J. The Aβ 3-Pyroglutamyl and 11-Pyroglutamyl Peptides Found in Senile Plaque Have Greater β-Sheet Forming and Aggregation Propensities in Vitro than Full-Length Aβ. Biochemistry 1999, 38, 10871–10877. [Google Scholar] [CrossRef] [PubMed]
- Gunn, A.P.; Masters, C.L.; Cherny, R.A. Pyroglutamate-Aβ: Role in the natural history of Alzheimer’s disease. Int. J. Biochem. Cell Biol. 2010, 42, 1915–1918. [Google Scholar] [CrossRef]
- Alexandru, A.; Jagla, W.; Graubner, S.; Becker, A.; Bäuscher, C.; Kohlmann, S.; Sedlmeier, R.; Raber, K.A.; Cynis, H.; Rönicke, R.; et al. Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aβ is induced by pyroglutamate-Aβ formation. J. Neurosci. 2011, 31, 12790–12801. [Google Scholar] [CrossRef] [PubMed]
- Dunkelmann, T.; Schemmert, S.; Honold, D.; Teichmann, K.; Butzküven, E.; Demuth, H.-U.; Shah, N.J.; Langen, K.-J.; Kutzsche, J.; Willbold, D.; et al. Comprehensive Characterization of the Pyroglutamate Amyloid-β Induced Motor Neurodegenerative Phenotype of TBA2.1 Mice. J. Alzheimer’s Dis. 2018, 63, 115–130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ameen-Ali, K.E.; Wharton, S.B.; Simpson, J.E.; Heath, P.R.; Sharp, P.; Berwick, J. Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 2017, 43, 553–570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Suenaga, T.; Hirano, A.; Llena, J.F.; Yen, S.H.; Dickson, D.W. Modified Bielschowsky stain and immunohistochemical studies on striatal plaques in Alzheimer’s disease. Acta Neuropathol. 1990, 80, 280–632. [Google Scholar] [CrossRef]
- Braak, H.; Braak, E. Alzheimer’s Disease: Striatal Amyloid Deposits and Neurofibrillary Changes. J. Neuropathol. Exp. Neurol. 1990, 49, 215–224. [Google Scholar] [CrossRef] [Green Version]
- Gearing, M.; Levey, A.I.; Mirra, S.S. Diffuse Plaques in the Striatum in Alzheimer Disease (AD): Relationship to the Striatal Mosaic and Selected Neuropeptide Markers. J. Neuropathol. Exp. Neurol. 1997, 56, 1363–1370. [Google Scholar] [CrossRef] [Green Version]
- Brilliant, M.J.; Elble, R.J.; Ghobrial, M.; Struble, R.G. The distribution of amyloid β protein deposition in the corpus striatum of patients with Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 1997, 23, 322–325. [Google Scholar] [CrossRef]
- Ryan, N.S.; Keihaninejad, S.; Shakespeare, T.J.; Lehmann, M.; Crutch, S.; Malone, I.B.; Thornton, J.; Mancini, L.; Hyare, H.; Yousry, T.; et al. Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain 2013, 136, 1399–1414. [Google Scholar] [CrossRef]
- Hanseeuw, B.J.; Lopera, F.; Sperling, R.A.; Norton, D.J.; Guzman-Velez, E.; Baena, A.; Pardilla-Delgado, E.; Schultz, A.P.; Gatchel, J.; Jin, D.; et al. Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer’s disease. Alzheimer’s Res. Ther. 2019, 11, 17. [Google Scholar] [CrossRef]
- Sofola-Adesakin, O.; Khericha, M.; Snoeren, I.; Tsuda, L.; Partridge, L. pGluAβ increases accumulation of Aβ in vivo and exacerbates its toxicity. Acta Neuropathol. Commun. 2016, 4, 109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dammers, C.; Schwarten, M.; Buell, A.K.; Willbold, D. Pyroglutamate-modified Aβ(3–42) affects aggregation kinetics of Aβ(1–42) by accelerating primary and secondary pathways. Chem. Sci. 2017, 8, 4996–5004. [Google Scholar] [CrossRef] [Green Version]
- Heneka, M.T.; Carson, M.J.; El Khoury, J.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; et al. Neuroinflammation in Alzheimer’s disease. Lancet. Neurol. 2015, 14, 388–405. [Google Scholar] [CrossRef] [Green Version]
- Tanila, H. Wading pools, fading memories—Place navigation in transgenic mouse models of Alzheimer’s disease. Front. Aging Neurosci. 2012, 4, 11. [Google Scholar] [CrossRef] [Green Version]
- Arendash, G.W.; Gordon, M.N.; Diamond, D.M.; Austin, L.A.; Hatcher, J.M.; Jantzen, P.; DiCarlo, G.; Wilcock, D.; Morgan, D. Behavioral Assessment of Alzheimer’s Transgenic Mice Following Long-Term Aβ Vaccination: Task Specificity and Correlations between Aβ Deposition and Spatial Memory. DNA Cell Biol. 2001, 20, 737–744. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, H.; Yan, H.; Tang, N.; Li, X.; Pang, P.; Li, H.; Chen, W.; Guo, Y.; Shu, S.; Cai, Y.; et al. Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses. Nat. Commun. 2017, 8, 1676. [Google Scholar] [CrossRef] [PubMed]
- Chen, G.; Chen, K.S.; Knox, J.; Inglis, J.; Bernard, A.; Martin, S.J.; Justice, A.; McConlogue, L.; Games, D.; Freedman, S.B.; et al. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 2000, 408, 975–979. [Google Scholar] [CrossRef] [PubMed]
- Dineley, K.T.; Kayed, R.; Neugebauer, V.; Fu, Y.; Zhang, W.; Reese, L.C.; Taglialatela, G. Amyloid-beta oligomers impair fear conditioned memory in a calcineurin-dependent fashion in mice. J. Neurosci. Res. 2010, 88, 2923–2932. [Google Scholar] [PubMed] [Green Version]
- Kittelberger, K.A.; Piazza, F.; Tesco, G.; Reijmers, L.G. Natural Amyloid-Beta Oligomers Acutely Impair the Formation of a Contextual Fear Memory in Mice. PLoS ONE 2012, 7, e29940. [Google Scholar] [CrossRef] [PubMed]
- Brown, M.W.; Aggleton, J.P. Recognition memory: What are the roles of the perirhinal cortex and hippocampus? Nat. Rev. Neurosci. 2001, 2, 51–61. [Google Scholar] [CrossRef] [PubMed]
- Deacon, R.M.; Rawlins, J.N. T-maze alternation in the rodent. Nat. Protoc. 2006, 1, 7–12. [Google Scholar] [CrossRef] [PubMed]
- Locchi, F.; Dall’Olio, R.; Gandolfi, O.; Rimondini, R. Water T-maze, an improved method to assess spatial working memory in rats: Pharmacological validation. Neurosci. Lett. 2007, 422, 213–216. [Google Scholar] [CrossRef] [PubMed]
- Izquierdo, I.; Furini, C.R.; Myskiw, J.C. Fear Memory. Physiol. Rev. 2016, 96, 695–750. [Google Scholar] [CrossRef] [Green Version]
- España, J.; Giménez-Llort, L.; Valero, J.; Miñano, A.; Rábano, A.; Rodriguez-Alvarez, J.; LaFerla, F.M.; Saura, C.A. Intraneuronal β-Amyloid Accumulation in the Amygdala Enhances Fear and Anxiety in Alzheimer’s Disease Transgenic Mice. Biol. Psychiatry 2010, 67, 513–521. [Google Scholar] [CrossRef]
- Hamann, S.; Monarch, E.S.; Goldstein, F.C. Impaired fear conditioning in Alzheimer’s disease. Neuropsychologia 2002, 40, 1187–1195. [Google Scholar] [CrossRef]
- Nasrouei, S.; Rattel, J.A.; Liedlgruber, M.; Marksteiner, J.; Wilhelm, F.H. Fear acquisition and extinction deficits in amnestic mild cognitive impairment and early Alzheimer’s disease. Neurobiol. Aging 2020, 87, 26–34. [Google Scholar] [CrossRef]
- Barnes, P.; Good, M. Impaired Pavlovian cued fear conditioning in Tg2576 mice expressing a human mutant amyloid precursor protein gene. Behav. Brain Res. 2005, 157, 107–117. [Google Scholar] [CrossRef]
- Knafo, S.; Venero, C.; Merino-Serrais, P.; Fernaud-Espinosa, I.; Gonzalez-Soriano, J.; Ferrer, I.; Santpere, G.; DeFelipe, J. Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer’s disease. J. Pathol. 2009, 219, 41–51. [Google Scholar] [CrossRef] [Green Version]
- Nussbaum, J.M.; Schilling, S.; Cynis, H.; Silva, A.; Swanson, E.; Wangsanut, T.; Tayler, K.; Wiltgen, B.; Hatami, A.; Rönicke, R.; et al. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature 2012, 485, 651–655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wittnam, J.L.; Portelius, E.; Zetterberg, H.; Gustavsson, M.K.; Schilling, S.; Koch, B.; Demuth, H.-U.; Blennow, K.; Wirths, O.; Bayer, T.A. Pyroglutamate amyloid β (Aβ) aggravates behavioral deficits in transgenic amyloid mouse model for Alzheimer disease. J. Biol. Chem. 2012, 287, 8154–8162. [Google Scholar] [CrossRef] [Green Version]
- Nagai, J.; Rajbhandari, A.K.; Gangwani, M.R.; Hachisuka, A.; Coppola, G.; Masmanidis, S.C.; Fanselow, M.S.; Khakh, B.S. Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell 2019, 177, 1280–1292.e20. [Google Scholar] [CrossRef] [PubMed]
- Miyakawa, T.; Yamada, M.; Duttaroy, A.; Wess, J. Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M1Muscarinic Acetylcholine Receptor. J. Neurosci. 2001, 21, 5239–5250. [Google Scholar] [CrossRef] [Green Version]
- Unger, E.L.; Eve, D.J.; Perez, X.A.; Reichenbach, D.K.; Xu, Y.; Lee, M.K.; Andrews, A.M. Locomotor hyperactivity and alterations in dopamine neurotransmission are associated with overexpression of A53T mutant human α-synuclein in mice. Neurobiol. Dis. 2006, 21, 431–443. [Google Scholar] [CrossRef] [PubMed]
- Castelli, M.; Federici, M.; Rossi, S.; De Chiara, V.; Napolitano, F.; Studer, V.; Motta, C.; Sacchetti, L.; Romano, R.; Musella, A.; et al. Loss of striatal cannabinoid CB1 receptor function in attention-deficit/hyperactivity disorder mice with point-mutation of the dopamine transporter. Eur. J. Neurosci. 2011, 34, 1369–1377. [Google Scholar] [CrossRef]
- Keszycki, R.M.; Fisher, D.W.; Dong, H. The Hyperactivity–Impulsivity–Irritiability–Disinhibition–Aggression–Agitation Domain in Alzheimer’s Disease: Current Management and Future Directions. Front. Pharmacol. 2019, 10, 1109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Balsters, J.H.; Zerbi, V.; Sallet, J.; Wenderoth, N.; Mars, R.B. Primate homologs of mouse cortico-striatal circuits. bioRxiv 2019, 9, 834481. [Google Scholar]
- Bonardi, C.; de Pulford, F.; Jennings, D.; Pardon, M.-C. A detailed analysis of the early context extinction deficits seen in APPswe/PS1dE9 female mice and their relevance to preclinical Alzheimer’s disease. Behav. Brain Res. 2011, 222, 89–97. [Google Scholar] [CrossRef] [PubMed]
- Maroof, N.; Ravipati, S.; Pardon, M.C.; Barrett, D.A.; Kendall, D.A. Reductions in endocannabinoid levels and enhanced coupling of cannabinoid receptors in the striatum are accompanied by cognitive impairments in the AβPPswe/PS1ΔE9 mouse model of Alzheimer’s disease. J. Alzheimer’s Dis. 2014, 42, 227–245. [Google Scholar] [CrossRef]
- Egan, K.; Vesterinen, H.; Beglopoulos, V.; Sena, E.; Macleod, M. From a mouse: Systematic analysis reveals limitations of experiments testing interventions in Alzheimer’s disease mouse models. Evid. Based Preclin. Med. 2016, 3, 12–23. [Google Scholar] [CrossRef] [PubMed]
- Veening-Griffioen, D.H.; Ferreira, G.S.; van Meer, P.J.K.; Boon, W.P.C.; Gispen-de Wied, C.C.; Moors, E.H.M.; Schellekens, H. Are some animal models more equal than others? A case study on the translational value of animal models of efficacy for Alzheimer’s disease. Eur. J. Pharmacol. 2019, 859, 172524. [Google Scholar] [CrossRef] [PubMed]
- Jankowsky, J.L.; Zheng, H. Practical considerations for choosing a mouse model of Alzheimer’s disease. Mol. Neurodegener. 2017, 12, 1–22. [Google Scholar] [CrossRef]
- Schemmert, S.; Schartmann, E.; Honold, D.; Zafiu, C.; Ziehm, T.; Langen, K.J.; Shah, N.J.; Kutzsche, J.; Willuweit, A.; Willbold, D. Deceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2. Neurobiol. Dis. 2019, 124, 36–45. [Google Scholar] [CrossRef]
- Schemmert, S.; Schartmann, E.; Zafiu, C.; Kass, B.; Hartwig, S.; Lehr, S.; Bannach, O.; Langen, K.-J.; Shah, N.J.; Kutzsche, J.; et al. Aβ Oligomer Elimination Restores Cognition in Transgenic Alzheimer’s Mice with Full-blown Pathology. Mol. Neurobiol. 2019, 56, 2211–2223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rogers, D.C.; Fisher, E.M.; Brown, S.D.; Peters, J.; Hunter, A.J.; Martin, J.E. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm. Genome Off. J. Int. Mamm. Genome Soc. 1997, 8, 711–713. [Google Scholar] [CrossRef]
- Dunkelmann, T.; Teichmann, K.; Ziehm, T.; Schemmert, S.; Frenzel, D.; Tusche, M.; Dammers, C.; Jürgens, D.; Langen, K.J.; Demuth, H.U.; et al. Aβ oligomer eliminating compounds interfere successfully with pEAβ(3–42) induced motor neurodegenerative phenotype in transgenic mice. Neuropeptides 2018, 67, 27–35. [Google Scholar] [CrossRef]
- Spowart-Manning, L.; Van der Staay, F. The T-maze continuous alternation task for assessing the effects of putative cognition enhancers in the mouse. Behav. Brain Res. 2004, 151, 37–46. [Google Scholar] [CrossRef]
- Curzon, P.; Rustay, N.R.; Browman, K.E. Frontiers in Neuroscience Cued and Contextual Fear Conditioning for Rodents. In Methods of Behavior Analysis in Neuroscience; Buccafusco, J.J., Ed.; Taylor & Francis Group, LLC.: Boca Raton, FL, USA, 2009. [Google Scholar]
- Morris, R. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 1984, 11, 47–60. [Google Scholar] [CrossRef]
Analysis | Age | Number of Mice/Genotype | ||||
---|---|---|---|---|---|---|
WT | TAPS | APP/PS1 | TBA 2.1 | |||
Histology | 6.4 ± 0.3 | - | 6 | 5 | 3 | |
9.2 ± 0.4 | - | 1 | 3 | 3 | ||
15.1 ± 0.4 | - | 5 | 3 | - | ||
18.0 ± 0.4 | - | 4 | 4 | 1 | ||
24.8 ± 1.3 | 5 | 6 | 5 | 5 | ||
SHIRPA | 4.1 ± 0.2 | 3 | 3 | - | - | |
5.5 ± 0.4 | 4 | 8 | - | - | ||
8.6 ± 0.4 | 8 | 18 | - | - | ||
12.5 ± 0.3 | 9 | 16 | - | - | ||
14.9 ± 0.2 | 7 | 11 | - | - | ||
17.6 ± 0.6 | 3 | 4 | - | - | ||
Open Field | 18.8 ± 0.7 | 8 | 4 | 5 | 8 | |
NOR | 18.8 ± 0.7 | 8 | 4 | 5 | 8 | |
T-maze | 18.4 ± 0.7 | 13 | 9 | 7 | 13 | |
20.7 ± 0.7 | 10 | 6 | 6 | 10 | ||
Fear Conditioning | Cued | 18.8 ± 0.7 | 8 | 4 | 4 | 8 |
Contextual | 18.8 ± 0.7 | 8 | 4 | 4 | 8 | |
20.8 ± 0.7 | 7 | 2 | 3 | 6 | ||
MWM | 20.7 ± 0.7 | 11 | 6 | 8 | 12 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Camargo, L.C.; Schöneck, M.; Sangarapillai, N.; Honold, D.; Shah, N.J.; Langen, K.-J.; Willbold, D.; Kutzsche, J.; Schemmert, S.; Willuweit, A. PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 7062. https://doi.org/10.3390/ijms22137062
Camargo LC, Schöneck M, Sangarapillai N, Honold D, Shah NJ, Langen K-J, Willbold D, Kutzsche J, Schemmert S, Willuweit A. PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2021; 22(13):7062. https://doi.org/10.3390/ijms22137062
Chicago/Turabian StyleCamargo, Luana Cristina, Michael Schöneck, Nivethini Sangarapillai, Dominik Honold, N. Jon Shah, Karl-Josef Langen, Dieter Willbold, Janine Kutzsche, Sarah Schemmert, and Antje Willuweit. 2021. "PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease" International Journal of Molecular Sciences 22, no. 13: 7062. https://doi.org/10.3390/ijms22137062
APA StyleCamargo, L. C., Schöneck, M., Sangarapillai, N., Honold, D., Shah, N. J., Langen, K. -J., Willbold, D., Kutzsche, J., Schemmert, S., & Willuweit, A. (2021). PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer’s Disease. International Journal of Molecular Sciences, 22(13), 7062. https://doi.org/10.3390/ijms22137062