QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 13, 2007, 27(24):6552-6562; doi:10.1523/JNEUROSCI.5173-06.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Rissman, R. A. Articles by Sawchenko, P. E. Search for Related Content PubMed PubMed Citation Articles by Rissman, R. A. Articles by Sawchenko, P. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB PYRROLE Medline Plus Health Information Stress

 Previous Article  |  Next Article 

Neurobiology of Disease
Corticotropin-Releasing Factor Receptors Differentially Regulate Stress-Induced Tau Phosphorylation

Robert A. Rissman,¹ Kuo-Fen Lee,² Wylie Vale,² and Paul E. Sawchenko¹

¹Laboratory of Neuronal Structure and Function and ²The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies and Foundation for Medical Research, La Jolla, California 92037

Correspondence should be addressed to either Robert A. Rissman or Paul E. Sawchenko, Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, Email: rrissman{at}salk.edu or Email: sawchenko{at}salk.edu

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.

Key words: Alzheimer's disease; antalarmin corticotropin-releasing factor; corticotropin-releasing hormone; hippocampus; restraint stress; tau phosphorylation

---

Received Nov. 29, 2006; revised May 10, 2007; accepted May 11, 2007.

Correspondence should be addressed to either Robert A. Rissman or Paul E. Sawchenko, Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, Email: rrissman{at}salk.edu or Email: sawchenko{at}salk.edu

This article has been cited by other articles:

				C. J. Rice, C. A. Sandman, M. R. Lenjavi, and T. Z. Baram A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress Endocrinology, October 1, 2008; 149(10): 4892 - 4900. [Abstract] [Full Text] [PDF]

				O. T Wolf and B. M Kudielka Stress, health and ageing: a focus on postmenopausal women Menopause Int, September 1, 2008; 14(3): 129 - 133. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help