| First Author | Rissman RA | Year | 2007 |
| Journal | J Neurosci | Volume | 27 |
| Issue | 24 | Pages | 6552-62 |
| PubMed ID | 17567816 | Mgi Jnum | J:122366 |
| Mgi Id | MGI:3714200 | Doi | 10.1523/JNEUROSCI.5173-06.2007 |
| Citation | Rissman RA, et al. (2007) Corticotropin-releasing factor receptors differentially regulate stress-induced tau phosphorylation. J Neurosci 27(24):6552-62 |
| abstractText | Hyperphosphorylation of the microtubule-associated protein tau is a key event in the development of Alzheimer's disease (AD) neuropathology. Acute stress can induce hippocampal tau phosphorylation (tau-P) in rodents, but the mechanisms and pathogenic relevance of this response are unclear. Here, we find that hippocampal tau-P elicited by an acute emotional stressor, restraint, was not affected by preventing the stress-induced rise in glucocorticoids but was blocked by genetic or pharmacologic disruption of signaling through the type 1 corticotropin-releasing factor receptor (CRFR1). Conversely, these responses were exaggerated in CRFR2-deficient mice. Parallel CRFR dependence was seen in the stress-induced activation of specific tau kinases. Repeated stress exposure elicited cumulative effects on tau-P and its sequestration in an insoluble, and potentially pathogenic, form. These findings support differential regulatory roles for CRFRs in an AD-relevant form of neuronal plasticity and may link datasets documenting alterations in the CRF signaling system in AD and implicating chronic stress as a risk factor in age-related neurological disorders. |
