| First Author | Guo Q | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 11 | Pages | 2678-91 |
| PubMed ID | 22336193 | Mgi Jnum | J:191170 |
| Mgi Id | MGI:5461130 | Doi | 10.1016/j.neurobiolaging.2012.01.002 |
| Citation | Guo Q, et al. (2012) Central CRF system perturbation in an Alzheimer's disease knockin mouse model. Neurobiol Aging 33(11):2678-91 |
| abstractText | Alzheimer's disease (AD) is often accompanied by changes in mood as well as increases in circulating cortisol levels, suggesting that regulation of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis is disturbed. Here, we show that amyloid precursor protein (APP) is endogenously expressed in important limbic, hypothalamic, and midbrain nuclei that regulate hypothalamic-pituitary-adrenal axis activity. Furthermore, in a knockin mouse model of AD that expresses familial AD (FAD) mutations of both APP with humanized amyloid beta (hAbeta), and presenilin 1 (PS1), in their endogenous patterns (APP/hAbeta/PS1 animals), corticotropin releasing factor (CRF) levels are increased in key stress-related nuclei, resting corticosteroid levels are elevated, and animals display increased anxiety-related behavior. Endocrine and behavioral phenotypes can be normalized by loss of 1 copy of CRF receptor type-1 (Crfr1), consistent with a perturbation of central CRF signaling in APP/hAbeta/PS1 animals. However, reductions in anxiety and corticosteroid levels conferred by heterozygosity of CRF receptor type-1 do not improve a deficit in working memory observed in APP/hAbeta/PS1 mice, suggesting that perturbations of the CRF system are not the primary cause of decreased cognitive performance. |
