| First Author | Quartey MO | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 511 |
| Issue | 2 | Pages | 454-459 |
| PubMed ID | 30803762 | Mgi Jnum | J:291180 |
| Mgi Id | MGI:6442792 | Doi | 10.1016/j.bbrc.2019.02.083 |
| Citation | Quartey MO, et al. (2019) Age- and sex-dependent profiles of APP fragments and key secretases align with changes in despair-like behavior and cognition in young APPSwe/Ind mice. Biochem Biophys Res Commun 511(2):454-459 |
| abstractText | Biological sex exerts distinct influences on brain levels of the beta-amyloid (Abeta) peptide in both clinical depression and Alzheimer disease (AD), yet studies in animal models focus primarily on males. We examined behavioral 'despair'/depression (using the tail-suspension test) and memory (using the novel object recognition task) in J20 (hAPPSwe/Ind) mice. Three month-old male (but not female) J20 mice exhibited less despair-like behavior, but more evidence of cognitive deficits. In young J20 mice, only soluble Abeta peptides -primarily Abeta(1-40)- were detected. There was no evidence of an effect on despair-like behavior in the six month-old J20 mice, although cognitive deficits were now evident in both sexes, and coincided with a greater proportion of the neurotoxic Abeta(1-42) species (in soluble as well as insoluble fractions). This age-dependent shift in Abeta peptide profile coincided with reduced expression of glycosylated species of ADAM-10 (alpha-secretase) and BACE1 (beta-secretase), and an increased co-immunoprecipitation of presenilin-1 with nicastrin (components of the gamma-secretase complex). Sex-dependent changes in depression-related monoaminergic, e.g. serotonin and dopamine (but not noradrenaline), systems were evident already in young J20 mice. It is critical to acknowledge that sex-dependent APP-related phenotypes might differentially influence modifiable depression-related monoaminergic signalling at some of the earliest pathological stages of clinical AD. |
