| First Author | Justice NJ | Year | 2015 |
| Journal | J Neurosci | Volume | 35 |
| Issue | 6 | Pages | 2612-23 |
| PubMed ID | 25673853 | Mgi Jnum | J:219875 |
| Mgi Id | MGI:5629894 | Doi | 10.1523/JNEUROSCI.3333-14.2015 |
| Citation | Justice NJ, et al. (2015) Posttraumatic stress disorder-like induction elevates beta-amyloid levels, which directly activates corticotropin-releasing factor neurons to exacerbate stress responses. J Neurosci 35(6):2612-23 |
| abstractText | Recent studies have found that those who suffer from posttraumatic stress disorder (PTSD) are more likely to experience dementia as they age, most often Alzheimer's disease (AD). These findings suggest that the symptoms of PTSD might have an exacerbating effect on AD progression. AD and PTSD might also share common susceptibility factors such that those who experience trauma-induced disease were already more likely to succumb to dementia with age. Here, we explored these two hypotheses using a mouse model of PTSD in wild-type and AD model animals. We found that expression of human familial AD mutations in amyloid precursor protein and presenilin 1 leads to sensitivity to trauma-induced PTSD-like changes in behavioral and endocrine stress responses. PTSD-like induction, in turn, chronically elevates levels of CSF beta-amyloid (Abeta), exacerbating ongoing AD pathogenesis. We show that PTSD-like induction and Abeta elevation are dependent on corticotropin-releasing factor (CRF) receptor 1 signaling and an intact hypothalamic-pituitary-adrenal axis. Furthermore, we show that Abeta species can hyperexcite CRF neurons, providing a mechanism by which Abeta influences stress-related symptoms and PTSD-like phenotypes. Consistent with Abeta causing excitability of the stress circuitry, we attenuate PTSD-like phenotypes in vivo by lowering Abeta levels during PTSD-like trauma exposure. Together, these data demonstrate that exposure to PTSD-like trauma can drive AD pathogenesis, which directly perturbs CRF signaling, thereby enhancing chronic PTSD symptoms while increasing risk for AD-related dementia. |
