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Title: | Differential regulation of axon outgrowth and reinnervation by neurotrophin-3 and neurotrophin-4 in the hippocampal formation | Authors: | Hechler, Daniel BOATO, Francesco Nitsch, Robert HENDRIX, Sven |
Issue Date: | 2010 | Publisher: | SPRINGER | Source: | EXPERIMENTAL BRAIN RESEARCH, 205 (2). p. 215-221 | Abstract: | In this study, we investigated the hypothesis whether neurotrophins have a differential influence on neurite growth from the entorhinal cortex depending on the presence or absence of hippocampal target tissue. We investigated organotypic brain slices derived from the entorhinal-hippocampal system to analyze the effects of endogenous and recombinant neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) on neurite outgrowth and reinnervation. In the reinnervation assay, entorhinal cortex explants of transgenic mice expressing enhanced green fluorescent protein (EGFP) were co-cultured with wild-type hippocampi under the influence of recombinant NT-3 and NT-4 (500 ng/ml). Both recombinant NT-3 and NT-4 significantly increased the growth of EGFP+ nerve fibers into the target tissue. Consistently, reinnervation of the hippocampi of NT-4(-/-) and NT-3(+/-)NT-4(-/-) mice was substantially reduced. In contrast, the outgrowth assay did not exhibit reduction in axon outgrowth of NT-4(-/-) or NT-3(+/-)NT-4(-/-) cortex explants, while the application of recombinant NT-3 (500 ng/ml) induced a significant increase in the neurite extension of cortex explants. Recombinant NT-4 had no effect. In summary, only recombinant NT-3 stimulates axon outgrowth from cortex explants, while both endogenous and recombinant NT-3 and NT-4 synergistically promote reinnervation of the denervated hippocampus. These results suggest that endogenous and exogenous NT-3 and NT-4 differentially influence neurite growth depending on the presence or absence of target tissue. | Notes: | [Boato, Francesco; Hendrix, Sven] Hasselt Univ, Dept Funct Morphol, B-3590 Diepenbeek, Belgium. [Boato, Francesco; Hendrix, Sven] Hasselt Univ, Inst Biomed, B-3590 Diepenbeek, Belgium. [Hechler, Daniel; Hendrix, Sven] Charite, Inst Cell Biol & Neurobiol, Ctr Anat, D-13353 Berlin, Germany. [Boato, Francesco; Nitsch, Robert] Johannes Gutenberg Univ Mainz, Inst Microscop Anat & Neurobiol, Univ Med Mainz, Mainz, Germany. sven.hendrix@uhasselt.be | Keywords: | NT-3; NT-4; Hippocampus; Dentate gyrus; K252a; EGFP;NT-3; NT-4; Hippocampus; Dentate gyrus; K252a; EGFP | Document URI: | http://hdl.handle.net/1942/11137 | ISSN: | 0014-4819 | e-ISSN: | 1432-1106 | DOI: | 10.1007/s00221-010-2355-7 | ISI #: | 000280596400007 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2011 |
Appears in Collections: | Research publications |
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