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 (61) Citing Articles via Google Scholar Google Scholar Articles by Giehl, K. M. Articles by Yan, Q. Search for Related Content PubMed PubMed Citation Articles by Giehl, K. M. Articles by Yan, Q.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 15, 1998, 18(18):7351-7360

The Survival-Promoting Effect of Glial Cell Line-Derived Neurotrophic Factor on Axotomized Corticospinal Neurons In Vivo Is Mediated by an Endogenous Brain-Derived Neurotrophic Factor Mechanism

Klaus M. Giehl¹, Andreas Schütte¹, Pedro Mestres¹, and Qiao Yan²

¹ Anatomisches Institut, Universität des Saarlandes, D-66421 Homburg/Saar, Germany, and ² Department of Neurobiology, Amgen Inc., Amgen Center, Thousand Oaks, California, 91320

Autocrine trophic functions of brain-derived neurotrophic factor (BDNF) have been proposed for many central neurons because this neurotrophin displays striking colocalization with its receptor trkB within the CNS. In the cortex, the distribution patterns of BDNF and trkB expression are almost identical. Corticospinal neurons (CSNs) are a major cortical long-distance projecting system. They are localized in layer V of the somatosensory cortex, and their axons project into the spinal cord where they contribute to the innervation of spinal motoneurons. We have shown recently that adult CSNs express trkB mRNA and are rescued from axotomy-induced death by BDNF treatment. Half of the axotomized CSNs survived without BDNF infusions. These findings raise the possibility that endogenous cortical BDNF is involved in the trophic support of this neuronal population. To test the hypothesis that endogenous cortical BDNF promotes survival of adult CSNs, we infused the BDNF-neutralizing affinity-purified antibody RAB to axotomized and unlesioned CSNs for 7 d. This treatment resulted in increased death of axotomized CSNs. Survival of unlesioned CSNs was not affected by RAB treatment. In situ hybridizations for BDNF and trkB mRNA revealed that virtually all CSNs express trkB, whereas only half of them express BDNF. Thus, autocrine/paracrine mechanisms are likely to contribute to the endogenous BDNF protection of axotomized CSNs. We have demonstrated previously that, in addition to BDNF, glial cell line-derived neurotrophic factor (GDNF) and neurotrophin 3 (NT-3) also rescue CSNs from axotomy-induced death. We now show that the rescuing by GDNF requires the presence of endogenous cortical BDNF, implicating a central role of this neurotrophin in the trophic support of axotomized CSNs and a trophic cross-talk between BDNF and GDNF regarding the maintenance of lesioned CSNs. In contrast, NT-3 promotes survival of axotomized CSNs even when endogenous cortical BDNF is neutralized by RAB, indicating a potential of compensatory mechanisms for the trophic support of CSNs.

Key words: corticospinal neurons; axotomy; neurotrophin; BDNF; GDNF; autocrine; paracrine; gene expression; neuronal protection

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18187351-10$05.00/0

This article has been cited by other articles:

				J. C. Dugas, W. Mandemakers, M. Rogers, A. Ibrahim, R. Daneman, and B. A. Barres A Novel Purification Method for CNS Projection Neurons Leads to the Identification of Brain Vascular Cells as a Source of Trophic Support for Corticospinal Motor Neurons J. Neurosci., August 13, 2008; 28(33): 8294 - 8305. [Abstract] [Full Text] [PDF]

				A. Shulga, J. Thomas-Crusells, T. Sigl, A. Blaesse, P. Mestres, M. Meyer, Q. Yan, K. Kaila, M. Saarma, C. Rivera, et al. Posttraumatic GABAA-Mediated [Ca2+]i Increase Is Essential for the Induction of Brain-Derived Neurotrophic Factor-Dependent Survival of Mature Central Neurons J. Neurosci., July 2, 2008; 28(27): 6996 - 7005. [Abstract] [Full Text] [PDF]

				J. W. Grau, E. D. Crown, A. R. Ferguson, S. N. Washburn, M. A. Hook, and R. C. Miranda Instrumental learning within the spinal cord: underlying mechanisms and implications for recovery after injury. Behav Cogn Neurosci Rev, December 1, 2006; 5(4): 191 - 239. [Abstract] [PDF]

				J. Villadiego, S. Mendez-Ferrer, T. Valdes-Sanchez, I. Silos-Santiago, I. Farinas, J. Lopez-Barneo, and J. J. Toledo-Aral Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body Cells In Situ and after Intrastriatal Transplantation J. Neurosci., April 20, 2005; 25(16): 4091 - 4098. [Abstract] [Full Text] [PDF]

				A. W. Harrington, B. Leiner, C. Blechschmitt, J. C. Arevalo, R. Lee, K. Morl, M. Meyer, B. L. Hempstead, S. O. Yoon, and K. M. Giehl From The Cover: Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury PNAS, April 20, 2004; 101(16): 6226 - 6230. [Abstract] [Full Text] [PDF]

				T. F. Oo, N. Kholodilov, and R. E. Burke Regulation of Natural Cell Death in Dopaminergic Neurons of the Substantia Nigra by Striatal Glial Cell Line-Derived Neurotrophic Factor In Vivo J. Neurosci., June 15, 2003; 23(12): 5141 - 5148. [Abstract] [Full Text] [PDF]

				H. Boukhaddaoui, V. Sieso, F. Scamps, and J. Valmier An Activity-Dependent Neurotrophin-3 Autocrine Loop Regulates the Phenotype of Developing Hippocampal Pyramidal Neurons before Target Contact J. Neurosci., November 15, 2001; 21(22): 8789 - 8797. [Abstract] [Full Text] [PDF]

				K. M. Giehl, S. Rohrig, H. Bonatz, M. Gutjahr, B. Leiner, I. Bartke, Q. Yan, L. F. Reichardt, C. Backus, A. A. Welcher, et al. Endogenous Brain-Derived Neurotrophic Factor and Neurotrophin-3 Antagonistically Regulate Survival of Axotomized Corticospinal Neurons In Vivo J. Neurosci., May 15, 2001; 21(10): 3492 - 3502. [Abstract] [Full Text] [PDF]

				J. T. Erickson, T. A. Brosenitsch, and D. M. Katz Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor Are Required Simultaneously for Survival of Dopaminergic Primary Sensory Neurons In Vivo J. Neurosci., January 15, 2001; 21(2): 581 - 589. [Abstract] [Full Text] [PDF]

				J. M. Canals, N. Checa, S. Marco, P. Akerud, A. Michels, E. Perez-Navarro, E. Tolosa, E. Arenas, and J. Alberch Expression of Brain-Derived Neurotrophic Factor in Cortical Neurons Is Regulated by Striatal Target Area J. Neurosci., January 1, 2001; 21(1): 117 - 124. [Abstract] [Full Text] [PDF]

				H. Hammarberg, O. Lidman, C. Lundberg, S. Y. Eltayeb, A. W. Gielen, S. Muhallab, A. Svenningsson, H. Linda, P. H. van der Meide, S. Cullheim, et al. Neuroprotection by Encephalomyelitis: Rescue of Mechanically Injured Neurons and Neurotrophin Production by CNS-Infiltrating T and Natural Killer Cells J. Neurosci., July 15, 2000; 20(14): 5283 - 5291. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help