Journal
NEUROSCIENCE
Volume 164, Issue 3, Pages 896-907Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2009.09.005
Keywords
aging; cellular prion protein (PrPC); behavior; acetylcholinesterase (AChE); synaptophysin; caspase-3
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
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The cellular prion protein (PrPC) is a neuronal-anchored glycoprotein that has been associated with various functions in the CNS such as synaptic plasticity, cognitive processes and neuroprotection. Here we investigated age-related behavioral and neurochemical alterations in wild-type (Prnp(+/+)), PrPC knockout (Prnp(0/0)) and the PrPC overexpressing Tg-20 mice. Three- or 11 month-old animals were submitted to a battery of behavioral tasks including open field, activity cages, elevated plus-maze, social recognition and inhibitory avoidance tasks. The 11 month-old Prnp(+/+) and Prnp(0/0) mice exhibited significant impairments in their locomotor activity and social recognition memory and increased anxiety-related responses. Remarkably, Tg-20 mice did not present these age-related impairments. The i.c.v. infusion of STI1 peptide 230-245, which includes the PrPC binding site, improved the age-related social recognition deficits in Prnp(+/+). In comparison with the two other age-matched genotypes, the 11 month-old Tg-20 mice also exhibited reduced activity of seric acetylcholinesterase, increased expression of the protein synaptophysin and decreased caspase-3 positive-cells in the hippocampus. The present findings obtained with genetic and pharmacological approaches provide convincing evidence that PrPC exerts a critical role in the age-related behavioral deficits in mice probably through adaptive mechanisms including apoptotic pathways and synaptic plasticity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
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