Cellular prion protein modulates age-related behavioral and neurochemical alterations in mice.
The cellular prion protein (PrP(C)) 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(+/+)), PrP(C) knockout (Prnp(0/0)) and the PrP(C) 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 PrP(C) 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 PrP(C) exerts a critical role in the age-related behavioral deficits in mice probably through adaptive mechanisms including apoptotic pathways and synaptic plasticity.
Rial
D
D
Departamento de Farmacologia, UFSC, Florianópolis, SC, Brazil.
Duarte
F S
FS
Xikota
J C
JC
Schmitz
A E
AE
Dafré
A L
AL
Figueiredo
C P
CP
Walz
R
R
Prediger
R D S
RD
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017209:Apoptosis / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D003704:Dementia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000494:pharmacology; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D016708:Synaptophysin / Q000378:metabolism
D010446:Peptide Fragments; D018621:PrPC Proteins; D016708:Synaptophysin; D000110:Acetylcholinesterase; C505409:Casp3 protein, mouse; D053148:Caspase 3