Fast and Sustained Axonal Growth by BDNF Released from Chitosan Microspheres

Brain-derived neurotrophic factor (BDNF) regulates dendritic branching and dendritic spine morphology, as well as synaptic plasticity and long-term potentiation. Consequently, BDNF deficiency has been associated with some neurological disorders such as Alzheimer's, Parkinson's or Huntington's diseases. In contrast, elevated BDNF levels correlate with recovery after traumatic central nervous system (CNS) injuries. The utility of BDNF as a therapeutic agent is limited by its short half-life in a pathological microenvironment and its low efficacy caused by unwanted consumption of non-neuronal cells or inappropriate dosing. Here, we tested the activity of chitosan microsphere-encapsulated BDNF to prevent clearance and prolong the efficacy of this neurotrophin. Neuritic growth activity of BDNF release from chitosan microspheres was observed in the PC12 rat pheochromocytoma cell line, which is dependent on neurotrophins to differentiate via the neurotrophin receptor (NTR). We obtained a rapid and sustained increase in neuritic out-growth of cells treated with BDNF-loaded chitosan microspheres over control cells (p < 0.001). The average of neuritic out-growth velocity was three times higher in the BDNF-loaded chitosan microspheres than in the free BDNF. We conclude that the slow release of BDNF from chitosan microspheres enhances signaling through NTR and promotes axonal growth in neurons, which could constitute an important therapeutic agent in neurodegenerative diseases and CNS lesions.

Automated summary

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in dendritic branching, dendritic spine morphology, synaptic plasticity, and long-term potentiation. Its deficiency is associated with neurodegenerative diseases, while elevated levels are linked to recovery after CNS injuries. To overcome the limitations of BDNF as a therapeutic agent, we tested the efficacy of chitosan microsphere-encapsulated BDNF. Our results demonstrate that slow release of BDNF from chitosan microspheres enhances neuritic growth and axonal growth, making it a potential therapeutic agent for neurodegenerative diseases and CNS lesions.