Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage

• Type of Material: Article
• Authors: Matthias Kreuzer, Technical University of Munich; Glenda Keating, Emory University; Thomas Fenzl, Technical University of Munich; Lorenz Haertner, Medical University of Innsbruck; Christopher G. Sinon, Emory University; Ihab Hajjar, Emory University; Vincent Ciavatta, Emory University; David Rye, Emory University; Paul Garcia, Emory University
• Language: English
• Date: 2020-12-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms21239290
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 21
• Issue: 23
• Start Page: 1
• End Page: 19
• Grant/Funding Information: This work was in part supported by Departmental Resources (M.K.), the James S. McDonnell Foundation (P.S.G.), NIH Grant NS089719 (D.B.R.), and NIH Grant R01 AG042127 (I.H.).
• Keywords: PERMUTATION ENTROPY; AGE; A-BETA; Alzheimer’ QUANTITATIVE EEG; Chemistry; Science & Technology; GLUTAMATE; Chemistry, Multidisciplinary; Physical Sciences; Biochemistry & Molecular Biology; DEMENTIA; COGNITIVE DECLINE; GABA(A) RECEPTORS; EFFECT SIZE; Life Sciences & Biomedicine; sleep architecture; s; ALZHEIMERS-DISEASE; electroencephalography
• Research Categories: Chemistry, Biochemistry; Chemistry, General; Biology, Molecular

Abstract

Transgenic modification of the two most common genes (APPsw, PS1∆E9) related to familial Alzheimer’s disease (AD) in rats has produced a rodent model that develops pathognomonic signs of AD without genetic tau-protein modification. We used 17-month-old AD rats (n = 8) and age-matched controls (AC, n = 7) to evaluate differences in sleep behavior and EEG features during wakefulness (WAKE), non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) over 24-h EEG recording (12:12h dark–light cycle). We discovered that AD rats had more sleep–wake transitions and an increased probability of shorter REM and NREM bouts. AD rats also expressed a more uniform distribution of the relative spectral power. Through analysis of information content in the EEG using entropy of difference, AD animals demonstrated less EEG information during WAKE, but more information during NREM. This seems to indicate a limited range of changes in EEG activity that could be caused by an AD-induced change in inhibitory network function as reflected by increased GABAAR-β2 expression but no increase in GAD-67 in AD animals. In conclusion, this transgenic rat model of Alzheimer’s disease demonstrates less obvious EEG features of WAKE during wakefulness and less canonical features of sleep during sleep.