BDNF Promotes the Regenerative Sprouting, But Not Survival, of Injured Serotonergic Axons in the Adult Rat Brain

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