| First Author | Rial D | Year | 2012 |
| Journal | Neuroscience | Volume | 215 |
| Pages | 79-89 | PubMed ID | 22537845 |
| Mgi Jnum | J:192442 | Mgi Id | MGI:5465086 |
| Doi | 10.1016/j.neuroscience.2012.04.034 | Citation | Rial D, et al. (2012) Overexpression of cellular prion protein (PrP(C)) prevents cognitive dysfunction and apoptotic neuronal cell death induced by amyloid-beta (Abeta(1)(-)(4)(0)) administration in mice. Neuroscience 215:79-89 |
| abstractText | 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-beta (Abeta) 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 Abeta(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 Abeta(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 Abeta(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 Abeta(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. |
