title: Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 1. Circadian changes.
abstract: Circadian disturbances, including a fragmented sleep-wake pattern and sundowning, are commonly reported early in the progression of Alzheimer's disease (AD). These changes are distinctly different from those observed in non-pathological aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. A novel triple-transgenic model of AD, 3xTg-AD, is the only model to exhibit both Abeta and tau pathology, and mimic human AD. The present study characterized changes pertaining to circadian rhythmicity that occur prior to and post-AD pathology. Both male and female 3xTg-AD mice demonstrated alterations to their circadian pacemaker with decreased nocturnal behavior when compared to controls. Specifically, males showed greater locomotor activity during the day and shorter freerunning periods prior to the onset of AD-pathology, and females had a decrease in activity levels during their typical active phase. Both sexes did not differ in terms of their freerunning periods or photic phase shifting ability. A decrease in vasoactive intestinal polypeptide-containing and vasopressin-containing cells was observed in the suprachiasmatic nucleus of 3xTg-AD mice relative to controls. This study demonstrates that abnormalities in circadian rhythmicity in 3xTg-AD mice precede expected AD pathology. This suggests that human studies may wish to determine if similar circadian dysfunction is predictive of early-onset AD.
authors.affiliation: Department of Psychology, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada T2N 1N4.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Sterniczuk
authors.forename: Richard H
authors.initials: RH
authors.lastname: Dyck
authors.forename: Frank M
authors.initials: FM
authors.lastname: Laferla
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D021081:Chronobiology Disorders / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics; D009414:Nerve Growth Factors / Q000378:metabolism; D053764:Presenilin-1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors; C508853:PSEN1 protein, human; D053764:Presenilin-1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014667:Vasopressins; D014660:Vasoactive Intestinal Peptide; D053829:Amyloid Precursor Protein Secretases