Unknown

Dataset Information

0

Targeting glucocorticoid receptors prevents the effects of early life stress on amyloid pathology and cognitive performance in APP/PS1 mice.


ABSTRACT: Exposure to chronic stress or elevated glucocorticoid hormone levels in adult life has been associated with cognitive deficits and an increased risk for Alzheimer's disease (AD). Since exposure to stress during early life enhances stress-responsiveness and lastingly affects cognition in adult life, we here investigated; (i) whether chronic early life stress (ELS) affects AD pathology and cognition in middle-aged APPswe/PS1dE9 mice, and (ii) whether it is still possible to rescue these late effects by briefly blocking glucocorticoid receptors (GRs) at a translationally relevant, middle age. Transgenic APPswe/PS1dE9 mice were subjected to ELS by housing dams and pups with limited nesting and bedding material from postnatal days 2-9 only. In 6- and 12-month-old offspring, this resulted in enhanced hippocampal amyloid-? (A?)-40 and -42 levels, and in reduced cognitive flexibility, that correlated well with the A?42 levels. In parallel, CORT levels and BACE1 levels were significantly elevated. Surprisingly, blocking GRs for only 3 days at 12 months of age reduced CORT levels, reduced hippocampal A?40 and -42, and ?-site APP-cleaving enzyme 1 (BACE1) levels, and notably rescued the cognitive deficits in 12-month-old APPswe/PS1dE9 mice. These mouse data demonstrate that exposure to stress during the sensitive period early in life influences later amyloid pathology and cognition in genetically predisposed, mutant mice, and as such, may increase AD vulnerability. The fact that a short treatment with a GR antagonist at middle age lastingly reduced A? levels and rescued the cognitive deficits after ELS, highlights the therapeutic potential of this drug for reducing amyloid pathology.

SUBMITTER: Lesuis SL 

PROVIDER: S-EPMC5830444 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Targeting glucocorticoid receptors prevents the effects of early life stress on amyloid pathology and cognitive performance in APP/PS1 mice.

Lesuis Sylvie L SL   Weggen Sascha S   Baches Sandra S   Lucassen Paul J PJ   Krugers Harm J HJ  

Translational psychiatry 20180301 1


Exposure to chronic stress or elevated glucocorticoid hormone levels in adult life has been associated with cognitive deficits and an increased risk for Alzheimer's disease (AD). Since exposure to stress during early life enhances stress-responsiveness and lastingly affects cognition in adult life, we here investigated; (i) whether chronic early life stress (ELS) affects AD pathology and cognition in middle-aged APPswe/PS1dE9 mice, and (ii) whether it is still possible to rescue these late effec  ...[more]

Similar Datasets

2024-09-30 | GSE235179 | GEO
| S-EPMC7359297 | biostudies-literature
| S-EPMC4731410 | biostudies-literature
| S-EPMC8600261 | biostudies-literature
| S-EPMC3292807 | biostudies-other
| S-EPMC4833143 | biostudies-other
2020-11-24 | GSE144746 | GEO
| S-EPMC6918606 | biostudies-literature
| S-EPMC6037844 | biostudies-literature
| S-EPMC3364340 | biostudies-literature