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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.
Neuroscience 2012; 215:79-89N

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.

Authors+Show Affiliations

Departamento de Farmacologia, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -