Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus

Anne M. Fagan, Steven T. Suhr, Carrie Phillipi, Daniel A. Peterson, David M. Holtzman, Fred H. Gage

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2499-2511
Number of pages13
JournalJournal of Neuroscience
Volume17
Issue number7
StatePublished - 1997
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 2
Cholinergic Agents
Hippocampus
Nerve Growth Factor
Intraventricular Infusions
Messenger RNA
Cholinergic Neurons
Neutralizing Antibodies
Astrocytes
Gene Expression
Neurons
Antibodies
Brain

Keywords

  • entorhinal cortex lesion
  • FGF-2
  • hippocampus
  • neurotrophin
  • NGF
  • sprouting

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fagan, A. M., Suhr, S. T., Phillipi, C., Peterson, D. A., Holtzman, D. M., & Gage, F. H. (1997). Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus. Journal of Neuroscience, 17(7), 2499-2511.

Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus. / Fagan, Anne M.; Suhr, Steven T.; Phillipi, Carrie; Peterson, Daniel A.; Holtzman, David M.; Gage, Fred H.

In: Journal of Neuroscience, Vol. 17, No. 7, 1997, p. 2499-2511.

Research output: Contribution to journalArticle

Fagan, AM, Suhr, ST, Phillipi, C, Peterson, DA, Holtzman, DM & Gage, FH 1997, 'Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus', Journal of Neuroscience, vol. 17, no. 7, pp. 2499-2511.
Fagan, Anne M. ; Suhr, Steven T. ; Phillipi, Carrie ; Peterson, Daniel A. ; Holtzman, David M. ; Gage, Fred H. / Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus. In: Journal of Neuroscience. 1997 ; Vol. 17, No. 7. pp. 2499-2511.
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