Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s40478-014-0175-x
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dc.title | Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: Rapid reversal by anti-Aß agents | |
dc.contributor.author | Qi, Y | |
dc.contributor.author | Klyubin, I | |
dc.contributor.author | Harney, S.C | |
dc.contributor.author | Hu, N.W | |
dc.contributor.author | Cullen, W.K | |
dc.contributor.author | Grant, M.K | |
dc.contributor.author | Steffen, J | |
dc.contributor.author | Wilson, E.N | |
dc.contributor.author | Do Carmo, S | |
dc.contributor.author | Remy, S | |
dc.contributor.author | Fuhrmann, M | |
dc.contributor.author | Ashe, K.H | |
dc.contributor.author | Cuello, A.C | |
dc.contributor.author | Rowan, M.J | |
dc.date.accessioned | 2020-10-30T01:56:39Z | |
dc.date.available | 2020-10-30T01:56:39Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Qi, Y, Klyubin, I, Harney, S.C, Hu, N.W, Cullen, W.K, Grant, M.K, Steffen, J, Wilson, E.N, Do Carmo, S, Remy, S, Fuhrmann, M, Ashe, K.H, Cuello, A.C, Rowan, M.J (2014). Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: Rapid reversal by anti-Aß agents. Acta Neuropathologica Communications 2 (1) : 175. ScholarBank@NUS Repository. https://doi.org/10.1186/s40478-014-0175-x | |
dc.identifier.issn | 20515960 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/182027 | |
dc.description.abstract | Long before synaptic loss occurs in Alzheimer's disease significant harbingers of disease may be detected at the functional level. Here we examined if synaptic long-term potentiation is selectively disrupted prior to extracellular deposition of Aß in a very complete model of Alzheimer's disease amyloidosis, the McGill-R-Thy1-APP transgenic rat. Longitudinal studies in freely behaving animals revealed an age-dependent, relatively rapid-onset and persistent inhibition of long-term potentiation without a change in baseline synaptic transmission in the CA1 area of the hippocampus. Thus the ability of a standard 200 Hz conditioning protocol to induce significant NMDA receptor-dependent short- and long-term potentiation was lost at about 3.5 months of age and this deficit persisted for at least another 2-3 months, when plaques start to appear. Consistent with in vitro evidence for a causal role of a selective reduction in NMDA receptor-mediated synaptic currents, the deficit in synaptic plasticity in vivo was associated with a reduction in the synaptic burst response to the conditioning stimulation and was overcome using stronger 400 Hz stimulation. Moreover, intracerebroventricular treatment for 3 days with an N-terminally directed monoclonal anti- human Aß antibody, McSA1, transiently reversed the impairment of synaptic plasticity. Similar brief treatment with the BACE1 inhibitor LY2886721 or the ?-secretase inhibitor MRK-560 was found to have a comparable short-lived ameliorative effect when tracked in individual rats. These findings provide strong evidence that endogenously generated human Aß selectively disrupts the induction of long-term potentiation in a manner that enables potential therapeutic options to be assessed longitudinally at the pre-plaque stage of Alzheimer's disease amyloidosis. © 2014 Qi et al.; licensee BioMed Central. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | amyloid beta protein | |
dc.subject | amyloid precursor protein | |
dc.subject | antibody | |
dc.subject | aspartic proteinase | |
dc.subject | Bace protein, rat | |
dc.subject | fused heterocyclic rings | |
dc.subject | MRK 560 | |
dc.subject | N-(3-(2-amino-4a,5,7,7a-tetrahydro-4H-furo(3,4-d)(1,3)thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide | |
dc.subject | picolinic acid derivative | |
dc.subject | secretase | |
dc.subject | sulfonamide | |
dc.subject | age | |
dc.subject | Alzheimer disease | |
dc.subject | animal | |
dc.subject | animal behavior | |
dc.subject | antagonists and inhibitors | |
dc.subject | disease model | |
dc.subject | drug effects | |
dc.subject | genetics | |
dc.subject | hippocampus | |
dc.subject | human | |
dc.subject | immunology | |
dc.subject | long term potentiation | |
dc.subject | male | |
dc.subject | metabolism | |
dc.subject | pathophysiology | |
dc.subject | physiology | |
dc.subject | rat | |
dc.subject | synaptic transmission | |
dc.subject | transgenic rat | |
dc.subject | Wistar rat | |
dc.subject | Age Factors | |
dc.subject | Alzheimer Disease | |
dc.subject | Amyloid beta-Peptides | |
dc.subject | Amyloid beta-Protein Precursor | |
dc.subject | Amyloid Precursor Protein Secretases | |
dc.subject | Animals | |
dc.subject | Antibodies | |
dc.subject | Aspartic Acid Endopeptidases | |
dc.subject | Behavior, Animal | |
dc.subject | Disease Models, Animal | |
dc.subject | Heterocyclic Compounds, 2-Ring | |
dc.subject | Hippocampus | |
dc.subject | Humans | |
dc.subject | Long-Term Potentiation | |
dc.subject | Male | |
dc.subject | Picolinic Acids | |
dc.subject | Rats | |
dc.subject | Rats, Transgenic | |
dc.subject | Rats, Wistar | |
dc.subject | Sulfonamides | |
dc.subject | Synaptic Transmission | |
dc.type | Article | |
dc.contributor.department | PHARMACOLOGY | |
dc.description.doi | 10.1186/s40478-014-0175-x | |
dc.description.sourcetitle | Acta Neuropathologica Communications | |
dc.description.volume | 2 | |
dc.description.issue | 1 | |
dc.description.page | 175 | |
Appears in Collections: | Elements Staff Publications |
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