BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain

Laura A. Mamounas, C. Anthony Altar, Mary E. Blue, David R. Kaplan, Lino Tessarollo, W. Ernest Lyons

Research output: Contribution to journalArticlepeer-review

265 Scopus citations


Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the adult brain and can prevent the severe loss of cortical 5-HT axons caused by the neurotoxin p-chloroamphetamine (PCA). However, it has not been determined whether BDNF promotes the survival of 5-HT axons during PCA-insult or facilitates their regenerative sprouting after injury. We show here that BDNF fails to protect most 5-HT axons from PCA-induced degeneration. Instead, chronic BDNF infusions markedly stimulate the sprouting of both intact and PCA-lesioned 5-HT axons, leading to a hyperinnervation at the neocortical infusion site. BDNF treatment promoted the regrowth of 5-HT axons when initiated up to a month after PCA administration. The sprouted axons persisted in cortex for at least 5 weeks after terminating exogenous BDNF delivery. BDNF also encouraged the regrowth of the 5-HT plexus in the hippocampus, but only in those lamina where 5-HT axons normally ramify. In addition, intracortical BDNF infusions induced a sustained local activation of the TrkB receptor. The dose-response profiles for BDNF to stimulate 5-HT sprouting and Trk signaling were remarkably similar, suggesting a physiological link between the two events; both responses were maximal at intermediate doses of BDNF but declined at higher doses ('inverted-U-shaped' dose-response curves). Underlying the downregulation of the Trk signal with excessive BDNF was a decline in full- length TrkB protein, but not truncated TrkB protein or TrkB mRNA levels. Thus, BDNF-TrkB signaling does not protect 5-HT neurons from axonal injury, but has a fundamental role in promoting the structural plasticity of these neurons in the adult brain.

Original languageEnglish (US)
Pages (from-to)771-782
Number of pages12
JournalJournal of Neuroscience
Issue number2
StatePublished - Jan 15 2000


  • Amphetamines
  • BDNF
  • Cerebral cortex
  • Neurotoxicity
  • Neurotrophin
  • P- chloroamphetamine
  • Serotonin
  • Sprouting
  • Structural plasticity
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)


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