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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 15, 2007, 27(33):8745-8756; doi:10.1523/JNEUROSCI.1002-07.2007

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 (4) Citing Articles via Google Scholar Google Scholar Articles by Fernandez, A. M. Articles by Torres-Aleman, I. Search for Related Content PubMed PubMed Citation Articles by Fernandez, A. M. Articles by Torres-Aleman, I.

 Previous Article  |  Next Article 

Neurobiology of Disease
Calcineurin in Reactive Astrocytes Plays a Key Role in the Interplay between Proinflammatory and Anti-Inflammatory Signals

Ana M. Fernandez, Silvia Fernandez, Paloma Carrero, Miguel Garcia-Garcia, and Ignacio Torres-Aleman

Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain

Correspondence should be addressed to I. Torres-Aleman, Cajal Institute, Consejo Superior de Investigaciones Científicas, Avenida Dr. Arce 37, 28002 Madrid, Spain. Email: torres{at}cajal.csic.es

Maladaptive inflammation is a major suspect in progressive neurodegeneration, but the underlying mechanisms are difficult to envisage in part because reactive glial cells at lesion sites secrete both proinflammatory and anti-inflammatory mediators. We now report that astrocytes modulate neuronal resilience to inflammatory insults through the phosphatase calcineurin. In quiescent astrocytes, inflammatory mediators such as tumor necrosis factor- (TNF-) recruits calcineurin to stimulate a canonical inflammatory pathway involving the transcription factors nuclear factor B (NFB) and nuclear factor of activated T-cells (NFAT). However, in reactive astrocytes, local anti-inflammatory mediators such as insulin-like growth factor I also recruit calcineurin but, in this case, to inhibit NFB/NFAT. Proof of concept experiments in vitro showed that expression of constitutively active calcineurin in astrocytes abrogated the inflammatory response after TNF- or endotoxins and markedly enhanced neuronal survival. Furthermore, regulated expression of constitutively active calcineurin in astrocytes markedly reduced inflammatory injury in transgenic mice, in a calcineurin-dependent manner. These results suggest that calcineurin forms part of a molecular pathway whereby reactive astrocytes determine the outcome of the neuroinflammatory process by directing it toward either its resolution or its progression.

Key words: calcineurin; neuroinflammation; astrocytes; inflammatory cytokines; insulin-like growth factor I; neuronal death

---

Received Nov. 8, 2006; revised May 29, 2007; accepted June 14, 2007.

Correspondence should be addressed to I. Torres-Aleman, Cajal Institute, Consejo Superior de Investigaciones Científicas, Avenida Dr. Arce 37, 28002 Madrid, Spain. Email: torres{at}cajal.csic.es

This article has been cited by other articles:

				M. A. Sama, D. M. Mathis, J. L. Furman, H. M. Abdul, I. A. Artiushin, S. D. Kraner, and C. M. Norris Interleukin-1{beta}-dependent Signaling between Astrocytes and Neurons Depends Critically on Astrocytic Calcineurin/NFAT Activity J. Biol. Chem., August 8, 2008; 283(32): 21953 - 21964. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help