An in vitro and in vivo study of early deficits in associative learning in transgenic mice that over-express a mutant form of human APP associated with Alzheimer's disease
| Autor: | Jesus Benavides, Georg Andrees Bohme, Elena Porras-García, Michel Laville, Raudel Sánchez-Campusano, Antonio Rodríguez-Moreno, José M. Delgado-García, Eduardo Domínguez-del-Toro, Véronique Blanchard |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Genetically modified mouse Transgene Conditioning Classical Hippocampus Mice Transgenic Stimulation Hippocampal formation Amyloid beta-Protein Precursor Mice Alzheimer Disease Reaction Time Amyloid precursor protein Animals Humans Evoked Potentials biology General Neuroscience Association Learning Eyelids Long-term potentiation Associative learning Disease Models Animal Mutation biology.protein Psychology Neuroscience |
| Zdroj: | European Journal of Neuroscience. 20:1945-1952 |
| ISSN: | 1460-9568 0953-816X |
| DOI: | 10.1111/j.1460-9568.2004.03643.x |
| Popis: | Transgenic mice over-expressing a mutated form of the human amyloid precursor protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's disease (V642I, so-called London mutation, hereafter APPLd2) and wild-type controls were studied at age periods (3 and 10 months) prior to the overt development of neuritic amyloid plaques. Both 3- and 10-month-old APPLd2 mice had reflex eyelid responses like those of controls, but only younger mice were able to acquire a classical conditioning of eyelid responses in a trace paradigm. In vitro studies on hippocampal slices showed that 10-month-old APPLd2 mice also presented deficits in paired-pulse facilitation and long-term potentiation, but presented a normal synaptic activation of CA1 pyramidal cells by the stimulation of Schaffer collaterals. It is proposed that definite functional changes may appear well in advance of noticeable structural alterations in this animal model of Alzheimer's disease, and that specific learning tasks could have a relevant diagnostic value. |
| Databáze: | OpenAIRE |
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