HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 39, 29076-29084, September 29, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/39/29076    most recent M604959200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Müller, M. R. Articles by Alzheimer, C. Search for Related Content PubMed PubMed Citation Articles by Müller, M. R. Articles by Alzheimer, C. Social Bookmarking                      What's this?

Transgenic Mice Expressing Dominant-negative Activin Receptor IB in Forebrain Neurons Reveal Novel Functions of Activin at Glutamatergic Synapses^*

Mischa Roland Müller, Fang Zheng, Sabine Werner¹², and Christian Alzheimer¹³

From the Institute of Cell Biology, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland and the Institute of Physiology, University of Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany

The transforming growth factor family member activin is an important regulator of development and tissue repair. It is strongly up-regulated after acute injury to the adult brain, and application of exogenous activin protects neurons in several lesion models. To explore the role of endogenous activin in the normal and acutely damaged brain, we generated transgenic mice expressing a dominant-negative activin receptor IB (dnActRIB) mutant in forebrain neurons. The functionality of the transgene was verified in vivo. Hippocampal neurons from dnActRIB mice were significantly more vulnerable to intracerebroventricular injection of the excitotoxin kainic acid than those from control littermates, indicating a crucial role of endogenous activin in the rescue of neurons from excitotoxic insult. Because dnActRIB is only expressed in neurons, but not in glial cells, activin affords protection at least in part through a direct action on endangered neurons. Unexpectedly, the transgenic mice also revealed a prominent novel role of activin in glutamatergic neurotransmission in the intact adult brain. Electrophysiologic examination of excitatory synapses onto CA1 pyramidal cells in hippocampal slices of dnActRIB mice showed a reduced NMDA current response, which was associated with impaired long term potentiation. This is the first demonstration that activin receptor signaling is essential to optimize the performance of neuronal circuits in the mature brain under physiological conditions.

Received for publication, May 23, 2006 , and in revised form, July 25, 2006.

^* This work was supported by the ETH Zurich, the Swiss National Science Foundation (Grant 3100A0-109340/1 (to S. W.)), the University of Kiel, and the Deutsche Forschungsgemeinschaft (SFB 391, TP A9 (to C. A.)). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Joint senior authors.

² To whom correspondence may be addressed: Institute of Cell Biology, ETH Zurich, Honggerberg, HPM D42, CH-8093 Zurich, Switzerland. E-mail: sabine.werner{at}cell.biol.ethz.ch. ³ To whom correspondence may be addressed: Institute of Physiology, University of Kiel, Olshausenstr. 40, D-24098 Kiel, Germany. E-mail: c.alzheimer{at}physiologie.uni-kiel.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Shoji-Kasai, H. Ageta, Y. Hasegawa, K. Tsuchida, H. Sugino, and K. Inokuchi Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics J. Cell Sci., November 1, 2007; 120(21): 3830 - 3837. [Abstract] [Full Text] [PDF]

				T. Hikida, H. Jaaro-Peled, S. Seshadri, K. Oishi, C. Hookway, S. Kong, D. Wu, R. Xue, M. Andrade, S. Tankou, et al. From the Cover: Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans PNAS, September 4, 2007; 104(36): 14501 - 14506. [Abstract] [Full Text] [PDF]