In situ expression of brain-derived neurotrophic factor or neurotrophin-3 promotes sprouting of cortical serotonergic axons following a neurotoxic lesion

M. H. Grider, L. A. Mamounas, Weidong Le, H. David Shine

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Neurotrophins promote sprouting and elongation of central nervous system (CNS) axons following injury. Consequently, it has been suggested that neurotrophins could be used to repair the CNS by inducing axonal sprouting from nearby intact axons, thereby compensating for the loss of recently injured axons. We tested whether long-term overexpression of neurotrophins in the rat cortex would induce sprouting of cortical serotonergic axons following a neurotoxic injury. After a single subcutaneous injection of para- chloroamphetamine (PCA; 9 mg/ml) that lesions the majority of serotonergic axons in the rat cortex, we injected adenoviral vectors containing cDNAs for brain-derived neurotrophic factor (Adv.BDNF), neurotrophin-3 (Adv.NT-3), or nerve growth factor (Adv.NGF) into the rat frontal cortex. Nine days later, we measured significant increases in the concentration of the respective neurotrophins surrounding the vector injection sites, as measured by ELISA. Immunohistochemical localization of serotonin revealed a four-fold increase in the density of serotonergic fibers surrounding the injection sites of Adv.BDNF and Adv.NT-3, corresponding to a 50% increase in cortical serotonin concentration, compared with a control vector containing the cDNA for enhanced green fluorescent protein (Adv.EGFP). In contrast, there was no difference in serotonergic fiber density or cortical serotonin concentration surrounding the injection of Adv.NGF compared with Adv.EGFP. These data demonstrate that localized overexpression of BDNF or NT-3, but not NGF, is sufficient to promote sprouting of serotonergic axons in the cortex following an experimental neurotoxic injury.

Original languageEnglish (US)
Pages (from-to)404-412
Number of pages9
JournalJournal of Neuroscience Research
Volume82
Issue number3
DOIs
StatePublished - Nov 1 2005

Keywords

  • Adenoviral vector
  • Axonal sprouting
  • Neurotrophin
  • Plasticity
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

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