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Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-β (Aβ₁₋₄₀) administration in mice.

Abstract

The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has been associated with several functions in the CNS such as synaptic plasticity, learning and memory and neuroprotection. There is great interest in understanding the role of PrP(C) in the deleterious effects induced by the central accumulation of amyloid-β (Aβ) peptides, a pathological hallmark of Alzheimer's disease, but the existent results are still controversial. Here we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Aβ(1-40) peptide (400pmol/mouse) on the spatial learning and memory performance as well as hippocampal cell death biomarkers in adult wild type (Prnp(+/+)), PrP(C) knockout (Prnp(0/0)) and the PrP(C) overexpressing Tg-20 mice. Tg-20 mice, which present a fivefold increase in PrP(C) expression in comparison to wild type mice, were resistant to the Aβ(1-40)-induced spatial learning and memory impairments as indicated by reduced escape latencies to find the platform and higher percentage of time spent in the correct quadrant during training and probe test sessions of the water maze task. The protection against Aβ(1-40)-induced cognitive impairments observed in Tg-20 mice was accompanied by a significant decrease in the hippocampal expression of the activated caspase-3 protein and Bax/Bcl-2 ratio as well as reduced hippocampal cell damage assessed by MTT and propidium iodide incorporation assays. These findings indicate that the overexpression of PrP(C) prevents Aβ(1-40)-induced spatial learning and memory deficits in mice and that this response is mediated, at least in part, by the modulation of programed cell death pathways.

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  • Authors+Show Affiliations

    ,

    Departamento de Farmacologia, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.

    , , , ,

    Source

    Neuroscience 215: 2012 Jul 26 pg 79-89

    MeSH

    Amyloid beta-Peptides
    Analysis of Variance
    Animals
    Apoptosis
    Caspase 3
    Cell Survival
    Cognition Disorders
    Gene Expression Regulation
    Hippocampus
    In Vitro Techniques
    Male
    Maze Learning
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Neurons
    Peptide Fragments
    Prion Proteins
    Prions
    Propidium
    Proto-Oncogene Proteins c-bcl-2
    Reaction Time
    Tetrazolium Salts
    Thiazoles
    bcl-2-Associated X Protein

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22537845

    Citation

    Rial, D, et al. "Overexpression of Cellular Prion Protein (PrP(C)) Prevents Cognitive Dysfunction and Apoptotic Neuronal Cell Death Induced By Amyloid-β (Aβ₁₋₄₀) Administration in Mice." Neuroscience, vol. 215, 2012, pp. 79-89.
    Rial D, Piermartiri TC, Duarte FS, et al. Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-β (Aβ₁₋₄₀) administration in mice. Neuroscience. 2012;215:79-89.
    Rial, D., Piermartiri, T. C., Duarte, F. S., Tasca, C. I., Walz, R., & Prediger, R. D. (2012). Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-β (Aβ₁₋₄₀) administration in mice. Neuroscience, 215, pp. 79-89. doi:10.1016/j.neuroscience.2012.04.034.
    Rial D, et al. Overexpression of Cellular Prion Protein (PrP(C)) Prevents Cognitive Dysfunction and Apoptotic Neuronal Cell Death Induced By Amyloid-β (Aβ₁₋₄₀) Administration in Mice. Neuroscience. 2012 Jul 26;215:79-89. PubMed PMID: 22537845.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-β (Aβ₁₋₄₀) administration in mice. AU - Rial,D, AU - Piermartiri,T C, AU - Duarte,F S, AU - Tasca,C I, AU - Walz,R, AU - Prediger,R D, Y1 - 2012/04/23/ PY - 2012/01/31/received PY - 2012/04/02/revised PY - 2012/04/07/accepted PY - 2012/4/28/entrez PY - 2012/4/28/pubmed PY - 2012/10/27/medline SP - 79 EP - 89 JF - Neuroscience JO - Neuroscience VL - 215 N2 - The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has been associated with several functions in the CNS such as synaptic plasticity, learning and memory and neuroprotection. There is great interest in understanding the role of PrP(C) in the deleterious effects induced by the central accumulation of amyloid-β (Aβ) peptides, a pathological hallmark of Alzheimer's disease, but the existent results are still controversial. Here we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Aβ(1-40) peptide (400pmol/mouse) on the spatial learning and memory performance as well as hippocampal cell death biomarkers in adult wild type (Prnp(+/+)), PrP(C) knockout (Prnp(0/0)) and the PrP(C) overexpressing Tg-20 mice. Tg-20 mice, which present a fivefold increase in PrP(C) expression in comparison to wild type mice, were resistant to the Aβ(1-40)-induced spatial learning and memory impairments as indicated by reduced escape latencies to find the platform and higher percentage of time spent in the correct quadrant during training and probe test sessions of the water maze task. The protection against Aβ(1-40)-induced cognitive impairments observed in Tg-20 mice was accompanied by a significant decrease in the hippocampal expression of the activated caspase-3 protein and Bax/Bcl-2 ratio as well as reduced hippocampal cell damage assessed by MTT and propidium iodide incorporation assays. These findings indicate that the overexpression of PrP(C) prevents Aβ(1-40)-induced spatial learning and memory deficits in mice and that this response is mediated, at least in part, by the modulation of programed cell death pathways. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/22537845/Overexpression_of_cellular_prion_protein__PrP_C___prevents_cognitive_dysfunction_and_apoptotic_neuronal_cell_death_induced_by_amyloid_β__Aβ₁₋₄₀__administration_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(12)00394-6 DB - PRIME DP - Unbound Medicine ER -