Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-15
pubmed:abstractText
In addition to the occurrence of numerous neurofibrillary tangles and A? plaques, neurogenesis and neuronal plasticity are markedly altered in Alzheimer disease (AD). Although the most popular therapeutic approach has been to inhibit neurodegeneration, another is to promote neurogenesis and neuronal plasticity by utilizing the regenerative capacity of the brain. Here we show that, in a transgenic mouse model of AD, 3xTg-AD mice, there was a marked deficit in neurogenesis and neuroplasticity, which occurred before the formation of any neurofibrillary tangles or A? plaques and was associated with cognitive impairment. Furthermore, peripheral administration of Peptide 6, an 11-mer, which makes an active region of ciliary neurotrophic factor (CNTF, amino acid residues 146-156), restored cognition by enhancing neurogenesis and neuronal plasticity in these mice. Although this treatment had no detectable effect on A? and tau pathologies in 9-month animals, it enhanced neurogenesis in dentate gyrus, reduced ectopic birth in the granular cell layer, and increased neuronal plasticity in the hippocampus and cerebral cortex. These findings, for the first time, demonstrate the possibility of therapeutic treatment of AD and related disorders by peripheral administration of a peptide corresponding to a biologically active region of CNTF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1432-0533
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
605-21
pubmed:meshHeading
pubmed-meshheading:20697724-Alzheimer Disease, pubmed-meshheading:20697724-Amyloid beta-Peptides, pubmed-meshheading:20697724-Animals, pubmed-meshheading:20697724-Blotting, Western, pubmed-meshheading:20697724-Brain, pubmed-meshheading:20697724-Chromatography, High Pressure Liquid, pubmed-meshheading:20697724-Ciliary Neurotrophic Factor, pubmed-meshheading:20697724-Cognition Disorders, pubmed-meshheading:20697724-Disease Models, Animal, pubmed-meshheading:20697724-Immunohistochemistry, pubmed-meshheading:20697724-Maze Learning, pubmed-meshheading:20697724-Memory, pubmed-meshheading:20697724-Mice, pubmed-meshheading:20697724-Mice, Transgenic, pubmed-meshheading:20697724-Neurofibrillary Tangles, pubmed-meshheading:20697724-Neurogenesis, pubmed-meshheading:20697724-Neuronal Plasticity, pubmed-meshheading:20697724-Neuroprotective Agents, pubmed-meshheading:20697724-Peptides, pubmed-meshheading:20697724-Plaque, Amyloid, pubmed-meshheading:20697724-Protein Structure, Secondary, pubmed-meshheading:20697724-tau Proteins
pubmed:year
2010
pubmed:articleTitle
Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting A? and tau pathologies in 3xTg-AD mice.
pubmed:affiliation
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, 10314, USA. julie.blanchard.ibr@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't