Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-2
pubmed:abstractText
Currently, no treatment can prevent the cognitive and motor decline associated with widespread neurodegeneration in prion disease. However, we previously showed that targeting endogenous neuronal prion protein (PrP(C)) (the precursor of its disease-associated isoform, PrP(Sc)) in mice with early prion infection reversed spongiform change and prevented clinical symptoms and neuronal loss. We now show that cognitive and behavioral deficits and impaired neurophysiological function accompany early hippocampal spongiform pathology. Remarkably, these behavioral and synaptic impairments recover when neuronal PrP(C) is depleted, in parallel with reversal of spongiosis. Thus, early functional impairments precede neuronal loss in prion disease and can be rescued. Further, they occur before extensive PrP(Sc) deposits accumulate and recover rapidly after PrP(C) depletion, supporting the concept that they are caused by a transient neurotoxic species, distinct from aggregated PrP(Sc). These data suggest that early intervention in human prion disease may lead to recovery of cognitive and behavioral symptoms.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0896-6273
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
325-35
pubmed:meshHeading
pubmed-meshheading:17270731-Animals, pubmed-meshheading:17270731-Axons, pubmed-meshheading:17270731-Behavior, Animal, pubmed-meshheading:17270731-Brain, pubmed-meshheading:17270731-Cognition Disorders, pubmed-meshheading:17270731-Discrimination (Psychology), pubmed-meshheading:17270731-Electrophysiology, pubmed-meshheading:17270731-Hippocampus, pubmed-meshheading:17270731-Immunohistochemistry, pubmed-meshheading:17270731-Long-Term Potentiation, pubmed-meshheading:17270731-Memory Disorders, pubmed-meshheading:17270731-Mice, pubmed-meshheading:17270731-Mice, Transgenic, pubmed-meshheading:17270731-Motor Activity, pubmed-meshheading:17270731-Muscle, Skeletal, pubmed-meshheading:17270731-Nesting Behavior, pubmed-meshheading:17270731-PrPC Proteins, pubmed-meshheading:17270731-Prion Diseases, pubmed-meshheading:17270731-Psychomotor Performance, pubmed-meshheading:17270731-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17270731-Synapses, pubmed-meshheading:17270731-Visual Perception
pubmed:year
2007
pubmed:articleTitle
Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice.
pubmed:affiliation
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom. g.mallucci@prion.ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't