title: 3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress.
abstract: Chronic stress may be a risk factor for developing Alzheimer's disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety, and hippocampal amyloid β-particle (Aβ), phosphorylated tau (ptau), and brain-derived neurotrophic factor (BDNF) levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6-week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased brain-derived neurotrophic factor levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rothman
authors.forename: Nathan
authors.initials: N
authors.lastname: Herdener
authors.forename: Simonetta
authors.initials: S
authors.lastname: Camandola
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Texel
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Cong
authors.forename: Bronwen
authors.initials: B
authors.lastname: Martin
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005215:Fasting; D005938:Glucocorticoids / Q000097:blood; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D012919:Social Behavior; D013315:Stress, Psychological / Q000503:physiopathology*; D013997:Time Factors; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D005938:Glucocorticoids; D007328:Insulin; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins