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 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 (66) Citing Articles via Google Scholar Google Scholar Articles by Fagan, A. M. Articles by Gage, F. H. Search for Related Content PubMed PubMed Citation Articles by Fagan, A. M. Articles by Gage, F. H.

 Previous Article  |  Next Article 

Volume 17, Number 7, Issue of April 1, 1997 pp. 2499-2511
Copyright ©1997 Society for Neuroscience

Endogenous FGF-2 Is Important for Cholinergic Sprouting in the Denervated Hippocampus

Received Sept. 10, 1996; revised Jan. 10, 1997; accepted Jan. 14, 1997.

Anne M. Fagan^1, , Steven T. Suhr^1, , Carrie A. Lucidi-Phillipi^1, , Daniel A. Peterson¹, David M. Holtzman², and Fred H. Gage¹

¹ Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, and ² Departments of Neurology, Molecular Biology and Pharmacology, and the Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110

To investigate the molecular mechanisms of cholinergic sprouting in the hippocampus after removal of entorhinal cortical inputs, we evaluated trophic factor gene expression in the denervated hippocampus. Despite the proposed role for nerve growth factor (NGF) in this sprouting, we observed no change in NGF mRNA or protein at several postlesion time points. In contrast, FGF-2 mRNA was increased within 16 hr. FGF-2 immunoreactivity was localized within GFAP-positive hypertrophic astrocytes distributed specifically within the denervated outer molecular layer after the lesion. To address the functional significance of this increase in FGF-2, we assessed the magnitude of cholinergic sprouting in animals receiving chronic intracerebroventricular infusions of neutralizing antibodies specific for FGF-2 and compared it with that observed in lesioned animals receiving infusate controls. Animals given FGF-2 antibodies displayed a marked reduction in cholinergic sprouting as compared with controls. In fact, many of these animals exhibited virtually no sprouting at all despite histological verification of complete lesions. These results suggest that endogenous FGF-2 promotes cholinergic axonal sprouting in the injured adult brain. Furthermore, immunocytochemical localization of receptors for FGF-2 (i.e., FGFR1) on projecting basal forebrain cholinergic neurons suggests that FGF-2 acts directly on these neurons to induce the lesion-induced sprouting response.

Key words: entorhinal cortex lesion; FGF-2; hippocampus; NGF; neurotrophin; sprouting

This article has been cited by other articles:

				H. Lee, S. J. Raiker, K. Venkatesh, R. Geary, L. A. Robak, Y. Zhang, H. H. Yeh, P. Shrager, and R. J. Giger Synaptic Function for the Nogo-66 Receptor NgR1: Regulation of Dendritic Spine Morphology and Activity-Dependent Synaptic Strength J. Neurosci., March 12, 2008; 28(11): 2753 - 2765. [Abstract] [Full Text] [PDF]

				E. Tassi, S. Walter, A. Aigner, R. H. Cabal-Manzano, R. Ray, P. J. Reier, and A. Wellstein Effects on neurite outgrowth and cell survival of a secreted fibroblast growth factor binding protein upregulated during spinal cord injury Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R775 - R783. [Abstract] [Full Text] [PDF]

				J. J. Ramirez, J. L. Caldwell, M. Majure, D. R. Wessner, R. L. Klein, E. M. Meyer, and M. A. King Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats J. Neurosci., April 1, 2003; 23(7): 2797 - 2803. [Abstract] [Full Text] [PDF]

				R. Dono Fibroblast growth factors as regulators of central nervous system development and function Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R867 - R881. [Abstract] [Full Text] [PDF]

				G. Szebenyi, E. W. Dent, J. L. Callaway, C. Seys, H. Lueth, and K. Kalil Fibroblast Growth Factor-2 Promotes Axon Branching of Cortical Neurons by Influencing Morphology and Behavior of the Primary Growth Cone J. Neurosci., June 1, 2001; 21(11): 3932 - 3941. [Abstract] [Full Text] [PDF]

				O. Raineteau, K. Fouad, P. Noth, M. Thallmair, and M. E. Schwab Functional switch between motor tracts in the presence of the mAb IN-1 in the adult rat PNAS, May 24, 2001; (2001) 111165498. [Abstract] [Full Text] [PDF]

				Y. D. Teng, I. Mocchetti, A. M. Taveira-DaSilva, R. A. Gillis, and J. R. Wrathall Basic Fibroblast Growth Factor Increases Long-Term Survival of Spinal Motor Neurons and Improves Respiratory Function after Experimental Spinal Cord Injury J. Neurosci., August 15, 1999; 19(16): 7037 - 7047. [Abstract] [Full Text] [PDF]

				Y. Tatebayashi, K. Iqbal, and I. Grundke-Iqbal Dynamic Regulation of Expression and Phosphorylation of Tau by Fibroblast Growth Factor-2 In Neural Progenitor Cells from Adult Rat Hippocampus J. Neurosci., July 1, 1999; 19(13): 5245 - 5254. [Abstract] [Full Text] [PDF]

				J. A. Watt, C. W. Moffet, X. Zhou, S. Short, J. P. Herman, and C. M. Paden Central Peptidergic Neurons Are Hyperactive during Collateral Sprouting and Inhibition of Activity Suppresses Sprouting J. Neurosci., March 1, 1999; 19(5): 1586 - 1598. [Abstract] [Full Text] [PDF]

				B. Shi, S. J. Rabin, C. Brandoli, and I. Mocchetti Dexamethasone Induces Hypertrophy of Developing Medial Septum Cholinergic Neurons: Potential Role of Nerve Growth Factor J. Neurosci., November 15, 1998; 18(22): 9326 - 9334. [Abstract] [Full Text] [PDF]

				H. M. Chao, R. R. Sakai, L. Y. Ma, and B. S. McEwen Adrenal Steroid Regulation of Neurotrophic Factor Expression in the Rat Hippocampus Endocrinology, July 1, 1998; 139(7): 3112 - 3118. [Abstract] [Full Text] [PDF]

				H. Neumann, T. Misgeld, K. Matsumuro, and H. Wekerle Neurotrophins inhibit major histocompatibility class II inducibility of microglia: Involvement of the p75 neurotrophin receptor PNAS, May 12, 1998; 95(10): 5779 - 5784. [Abstract] [Full Text] [PDF]

				Y. Sun, S. Wu, G. Bu, M. K. Onifade, S. N. Patel, M. J. LaDu, A. M. Fagan, and D. M. Holtzman Glial Fibrillary Acidic Protein-Apolipoprotein E (apoE) Transgenic Mice: Astrocyte-Specific Expression and Differing Biological Effects of Astrocyte-Secreted apoE3 and apoE4 Lipoproteins J. Neurosci., May 1, 1998; 18(9): 3261 - 3272. [Abstract] [Full Text] [PDF]

				A. M. Fagan, M. Garber, M. Barbacid, I. Silos-Santiago, and D. M. Holtzman A Role for TrkA during Maturation of Striatal and Basal Forebrain Cholinergic Neurons In Vivo J. Neurosci., October 15, 1997; 17(20): 7644 - 7654. [Abstract] [Full Text] [PDF]

				O. Raineteau, K. Fouad, P. Noth, M. Thallmair, and M. E. Schwab Functional switch between motor tracts in the presence of the mAb IN-1 in the adult rat PNAS, June 5, 2001; 98(12): 6929 - 6934. [Abstract] [Full Text] [PDF]

				J. J. Ramirez, K. Bulsara, S. C. Moore, K. Ruch, and W. Abrams Progressive Unilateral Damage of the Entorhinal Cortex Enhances Synaptic Efficacy of the Crossed Entorhinal Afferent to Dentate Granule Cells J. Neurosci., November 15, 1999; 19(22): RC42 - RC42. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help