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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) 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 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 Web of Science (52) Citing Articles via Google Scholar Google Scholar Articles by Theis, M. Articles by Willecke, K. Search for Related Content PubMed PubMed Citation Articles by Theis, M. Articles by Willecke, K.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 1, 2003, 23(3):766

Accelerated Hippocampal Spreading Depression and Enhanced Locomotory Activity in Mice with Astrocyte-Directed Inactivation of Connexin43

Martin Theis¹, Regina Jauch², Lang Zhuo³, Dina Speidel¹, Anke Wallraff⁵, Britta Döring¹, Christian Frisch⁴, Goran Söhl¹, Barbara Teubner¹, Carsten Euwens¹, Joseph Huston⁴, Christian Steinhäuser⁵, Albee Messing³, Uwe Heinemann², and Klaus Willecke¹

¹ Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, D-53117 Bonn, Germany, ² Institut für Neurophysiologie der Charité, Abteilung Neurophysiologie, D-10117 Berlin, Germany, ³ Waisman Center and School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53705-2280, ⁴ Institut für Physiologische Psychologie, Universität Düsseldorf, D-40225 Düsseldorf, Germany, and ⁵ Experimental Neurobiology, Neurosurgery, University of Bonn, D-53105 Bonn, Germany

Using a human glial fibrillary acidic protein (hGFAP) promoter-driven cre transgene, we have achieved efficient inactivation of a floxed connexin43 (Cx43) gene in astrocytes of adult mice. The loss of Cx43 expression was monitored in a cell-autonomous manner via conditional replacement of the Cx43-coding region by a lacZ reporter gene. In this way, we bypassed the early postnatal lethality previously reported for Cx43 null mice and characterized the phenotypic consequences of Cx43 deficiency in the CNS. Mice lacking Cx43 in astrocytes were viable and showed no evidence of either neurodegeneration or astrogliosis. Spreading depression (SD) is a pathophysiological phenomenon observed in the CNS that is characterized by a propagating wave of depolarization followed by neuronal inactivation. Inhibitors of gap junctional communication have previously been shown to block initiation and propagation of SD. In contrast, we observed an increase in the velocity of hippocampal SD in the stratum radiatum of mice lacking Cx43 in astrocytes. In the same brain subregion, dye-coupling experiments revealed a reduction in overall astrocytic intercellular communication by ~50%. This strongly suggests separate and different neuronal and glial contributions of gap junctional intercellular communication to SD. Concomitant with increased velocity of spreading depression, we observed enhanced locomotory activity in mice lacking Cx43 in astrocytes.

Key words: Cx43; Cre/loxP; spreading depression; behavior; dye coupling; hippocampal astrocytes

---

Copyright © 2003 Society for Neuroscience  0270-6474/03/233766-11$05.00/0

This article has been cited by other articles:

				A. Kunze, M. R. Congreso, C. Hartmann, A. Wallraff-Beck, K. Huttmann, P. Bedner, R. Requardt, G. Seifert, C. Redecker, K. Willecke, et al. Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus PNAS, July 7, 2009; 106(27): 11336 - 11341. [Abstract] [Full Text] [PDF]

				S. E. Lutz, Y. Zhao, M. Gulinello, S. C. Lee, C. S. Raine, and C. F. Brosnan Deletion of Astrocyte Connexins 43 and 30 Leads to a Dysmyelinating Phenotype and Hippocampal CA1 Vacuolation J. Neurosci., June 17, 2009; 29(24): 7743 - 7752. [Abstract] [Full Text] [PDF]

				C. G. Schipke, B. Haas, and H. Kettenmann Astrocytes Discriminate and Selectively Respond to the Activity of a Subpopulation of Neurons within the Barrel Cortex Cereb Cortex, October 1, 2008; 18(10): 2450 - 2459. [Abstract] [Full Text] [PDF]

				M. A. Ozog, G. Modha, J. Church, R. Reilly, and C. C. Naus Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth J. Biol. Chem., March 7, 2008; 283(10): 6546 - 6560. [Abstract] [Full Text] [PDF]

				J. H.-C. Lin, N. Lou, N. Kang, T. Takano, F. Hu, X. Han, Q. Xu, D. Lovatt, A. Torres, K. Willecke, et al. A Central Role of Connexin 43 in Hypoxic Preconditioning J. Neurosci., January 16, 2008; 28(3): 681 - 695. [Abstract] [Full Text] [PDF]

				D. J. Chung, C. H. M. Castro, M. Watkins, J. P. Stains, M. Y. Chung, V. L. Szejnfeld, K. Willecke, M. Theis, and R. Civitelli Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 J. Cell Sci., October 15, 2006; 119(20): 4187 - 4198. [Abstract] [Full Text] [PDF]

				A. Wallraff, R. Kohling, U. Heinemann, M. Theis, K. Willecke, and C. Steinhauser The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J. Neurosci., May 17, 2006; 26(20): 5438 - 5447. [Abstract] [Full Text] [PDF]

				B. Haas, C. G. Schipke, O. Peters, G. Sohl, K. Willecke, and H. Kettenmann Activity-dependent ATP-waves in the Mouse Neocortex are Independent from Astrocytic Calcium Waves Cereb Cortex, February 1, 2006; 16(2): 237 - 246. [Abstract] [Full Text] [PDF]

				D. A. Iacobas, S. Iacobas, W. E. I. Li, G. Zoidl, R. Dermietzel, and D. C. Spray Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart Physiol Genomics, February 10, 2005; 20(3): 211 - 223. [Abstract] [Full Text] [PDF]

				M. A. Ozog, S. M. Bernier, D. C. Bates, B. Chatterjee, C. W. Lo, and C. C.G. Naus The Complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor Receptor {alpha} Up-Regulates Connexin43 and Intercellular Coupling in Astrocytes via the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription Pathway Mol. Biol. Cell, November 1, 2004; 15(11): 4761 - 4774. [Abstract] [Full Text] [PDF]

				Y. Ohkubo, A. O. Uchida, D. Shin, J. Partanen, and F. M. Vaccarino Fibroblast Growth Factor Receptor 1 Is Required for the Proliferation of Hippocampal Progenitor Cells and for Hippocampal Growth in Mouse J. Neurosci., July 7, 2004; 24(27): 6057 - 6069. [Abstract] [Full Text] [PDF]

				T. Nakase, G. Sohl, M. Theis, K. Willecke, and C. C.G. Naus Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes Am. J. Pathol., June 1, 2004; 164(6): 2067 - 2075. [Abstract] [Full Text] [PDF]

				B. Scheffler, T. Schmandt, W. Schroder, B. Steinfarz, L. Husseini, J. Wellmer, G. Seifert, K. Karram, H. Beck, I. Blumcke, et al. Functional network integration of embryonic stem cell-derived astrocytes in hippocampal slice cultures Development, November 15, 2003; 130(22): 5533 - 5541. [Abstract] [Full Text] [PDF]

				O. Peters, C. G. Schipke, Y. Hashimoto, and H. Kettenmann Different Mechanisms Promote Astrocyte Ca2+ Waves and Spreading Depression in the Mouse Neocortex J. Neurosci., October 29, 2003; 23(30): 9888 - 9896. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help