help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, B.
Right arrow Articles by Trojanowski, J. Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, B.
Right arrow Articles by Trojanowski, J. Q.
(American Journal of Pathology. 2005;167:1361-1369.)
© 2005 American Society for Investigative Pathology

Impaired Rapid Eye Movement Sleep in the Tg2576 APP Murine Model of Alzheimer’s Disease with Injury to Pedunculopontine Cholinergic Neurons

Bin Zhang*, Sigrid C. Veasey{dagger}, Marcelo A. Wood§, Lewis Z. Leng*, Christine Kaminski*, Susan Leight*, Ted Abel§, Virginia M.-Y. Lee* and John Q. Trojanowski*

From the Department of Pathology and Laboratory Medicine, and Institute on Aging, The Center for Neurodegenerative Disease Research;* the Center for Sleep and Respiratory Neurobiology; the Department of Medicine,{ddagger} Division of Sleep Medicine;{dagger} and the Department of Biology,§ The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

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 ß-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 Aß injury provides an invaluable tool with which to understand mechanisms of sleep/wake perturbations in Alzheimer’s disease.




This article has been cited by other articles:


Home page
 J. Neurophysiol.Home page
S. Datta
Activation of Pedunculopontine Tegmental PKA Prevents GABAB Receptor Activation-Mediated Rapid Eye Movement Sleep Suppression in the Freely Moving Rat
J Neurophysiol, June 1, 2007; 97(6): 3841 - 3850.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. S. Bandyopadhya, S. Datta, and S. Saha
Activation of pedunculopontine tegmental protein kinase a: a mechanism for rapid eye movement sleep generation in the freely moving rat.
J. Neurosci., August 30, 2006; 26(35): 8931 - 8942.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.