title: Human ApoE ε4 alters circadian rhythm activity, IL-1β, and GFAP in CRND8 mice.
abstract: Disruptions to daily living, inflammation, and astrogliosis are characteristics of Alzheimer's disease. Thus, circadian rhythms, nest construction, IL-1β and TNF-α, and glial fibrillary acidic protein (GFAP) were examined in a mouse model developed to model late-onset Alzheimer's disease-the most common form of the disease. Mice carrying both the mutated human AβPP transgene found in the CRND8 mouse and the human apolipoprotein E ε4 allele (CRND8/E4) were compared with CRND8 mice and wildtype (WT) mice. Circadian rhythms were evaluated by wheel-running behavior. Activity of daily living was measured by nest construction. This study then examined mRNA levels of the inflammatory cytokines IL-1β and TNF-α as well as protein levels of GFAP. Behavioral outcomes were then correlated with cytokines and GFAP. Compared to WT controls, both CRND8 and CRND8/E4 mice showed significantly more frequent, but shorter, bouts of activity. In the three groups, the CRND8/E4 mice had intermediate disruptions in circadian rhythms. Both CRND8/E4 mice and CRND8 mice showed significant impairments in nesting behavior compared to WTs. While CRND8 mice expressed significantly increased IL-1β and GFAP expression compared to WT controls, CRND8/E4 mice expressed intermediate IL-1β and GFAP levels. Significant correlations between IL-1β, GFAP, and behavior were observed. These data are congruent with other studies showing that human ApoE ε4 is protective early in life in transgenic mice modeling Alzheimer's disease.
authors.affiliation: Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Graybeal
authors.affiliation: Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: P Lorenzo
authors.initials: PL
authors.lastname: Bozzelli
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA, USA.
authors.forename: Lacey L
authors.initials: LL
authors.lastname: Graybeal
authors.affiliation: Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Groeber
authors.affiliation: Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: McKnight
authors.affiliation: School of Systems Biology, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cox
authors.affiliation: Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Flinn
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009425:Nesting Behavior / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012420:Running / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Alzheimer's disease; IL-1β; TNF-α; apolipoprotein E4; circadian rhythm; cytokines; glial fibrillary acidic protein; gliosis; nesting behavior; transgenic mice