Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression

Angelo, Marco; Plattner, Florian; Irvine, Elaine E.; Giese, K. Peter

doi:10.1046/j.1460-9568.2003.02746.x

Cited by 83Alzheimer's disease research and treatmentsMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression

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Angelo, Marco, Plattner, Florian, Irvine, Elaine E., Giese, K. Peter·2003·European Journal of Neuroscience

DOI 10.1046/j.1460-9568.2003.02746.x

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Abstract

Cleavage of the cyclin-dependent kinase 5 activator p35 generates the protein fragment p25, which accumulates in the forebrain of patients with Alzheimer's disease. Although p25 expression has been suggested to affect learning and memory, this hypothesis has not been tested to date. To investigate the role of p25 in hippocampus-dependent learning and memory we have generated transgenic mice expressing p25 preferentially in postnatal forebrain. p25 expression was highest in hippocampus where it averaged approximately 33% of endogenous p35 expression. This low level of p25 expression did not seem to result in hyperphosphorylation of tau, but increased the phosphorylation of neurofilament M and enhanced the expression of tau protein. These molecular changes did not correlate with neurodegeneration or motor abnormalities. In the Morris water maze the p25 mutants were normal in learning an initial platform location, but surprisingly reversal learning was improved when the platform position was changed. The p25 mutants were normal in contextual fear conditioning. However, when trained with a tone presentation the mutants showed reduced contextual conditioning and enhanced tone fear conditioning. We conclude that low p25 expression has pleiotropic effects on learning and memory. As p25 expression can improve learning and memory, p25 formation could be a compensatory mechanism for learning and memory deficits in Alzheimer's disease.

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Many different AD mouse models have shown impairment in reversal learning.
“Similarly, many different AD mouse models have shown impairment in reversal learning (Angelo et al., 2003; Dong et al., 2005; Filali et al., 2012; Cheng et al., 2013; Musilli et al., 2013; Papadopoulos et al., 2013).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Angelo et al., 2003

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Sexual dimorphisms in the effect of low‐level p25 expression on synaptic plasticity and memory
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Authors: Angelo, M., Plattner, F., Irvine, E. E., & Giese, K. P.
Affiliations: University College London (GB)
Corresponding author: Giese, K. Peter
ORCID: Plattner, Florian
Irvine, Elaine E.
Giese, K. Peter
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2003-07
Volume: 18
Issue: 2
Pages: 423-431
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1046/j.1460-9568.2003.02746.x
OpenAlex: W2000685126
Cited by: 82
References: 39
Citations by year: 2025: 1 · 2024: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 1 · 2014: 7 · 2013: 2 · 2012: 4
FWCI: 4.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 21 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Directorate for Biological Sciences
Medical Research Council
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: p25, cyclin-dependent kinase 5, Alzheimer's disease, reversal learning, fear conditioning, hippocampus-dependent learning, transgenic mice, regional gene expression, tau protein, learning and memory
MeSH terms: Alzheimer Disease, Animals, Brain, Conditioning, Psychological, Fear, Female, Male, Memory, Mice, Transgenic, Mutation, Phosphorylation, Reversal Learning, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, Gene Products, gag, tau Proteins, Neurofilament Proteins, Maze Learning, Models, Animal, Mice, gag Gene Products, Human Immunodeficiency Virus

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Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression

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