Journal article
Impaired Rapid Eye Movement Sleep in the Tg2576 APP Murine Model of Alzheimer’s Disease with Injury to Pedunculopontine Cholinergic Neurons
The American journal of pathology, Vol.167(5), pp.1361-1369
11/2005
DOI: 10.1016/S0002-9440(10)61223-0
PMCID: PMC1603771
PMID: 16251420
Abstract
Impaired rapid eye movement sleep (REMS) is commonly observed in Alzheimer’s disease, suggesting injury to mesopontine cholinergic neurons. We sought to determine whether abnormal β-amyloid peptides impair REMS and injure mesopontine cholinergic neurons in transgenic (hAPP695.SWE) mice (Tg2576) that model brain amyloid pathologies. Tg2576 mice and wild-type littermates were studied at 2, 6, and 12 months by using sleep recordings, contextual fear conditioning, and immunohistochemistry. At 2 months of age, REMS was indistinguishable by genotype but was reduced in Tg2576 mice at 6 and 12 months. Choline acetyltransferase-positive neurons in the pedunculopontine tegmentum of Tg2576 mice at 2 months evidenced activated caspase-3 immunoreactivity, and at 6 and 12 months the numbers of pedunculopontine tegmentum choline acetyltransferase-positive neurons were reduced in the Tg2576 mice. Other cholinergic groups involved in REMS were unperturbed. At 12 months, Tg2576 mice demonstrated increased 3-nitrotyrosine immunoreactivity in cholinergic projection sites but not in cholinergic soma. We have identified a population of selectively compromised cholinergic neurons in young Tg2576 mice that manifest early onset REMS impairment. The differential vulnerability of these cholinergic neurons to Aβ injury provides an invaluable tool with which to understand mechanisms of sleep/wake perturbations in Alzheimer’s disease.
Details
- Title: Subtitle
- Impaired Rapid Eye Movement Sleep in the Tg2576 APP Murine Model of Alzheimer’s Disease with Injury to Pedunculopontine Cholinergic Neurons
- Creators
- Bin Zhang - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchSigrid C Veasey - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchMarcelo A Wood - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchLewis Z Leng - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchChristine Kaminski - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchSusan Leight - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchTed Abel - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchVirginia M.-Y Lee - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease ResearchJohn Q Trojanowski - From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease Research
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.167(5), pp.1361-1369
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.1016/S0002-9440(10)61223-0
- PMID
- 16251420
- PMCID
- PMC1603771
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Language
- English
- Date published
- 11/2005
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065738602771
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