Study of BDNF Transcytosis in Hippocampal Neurons

Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays important roles in neuron survival, development and synaptic efficacy. It is believed that exogenous BDNF binding to TrkB activates three major signaling pathways: MAPK, PI3K and PLC-gamma. One important issue under these regulation mechanisms is whether and how BDNF is transported into neurons and its intracellular translocation. Furthermore, whether such exogenous BDNF is released and taken up by another neuron and involved in neuron to neuron communication has not been studied. In this work, BDNF conjugated to quantum dot is traced after it is taken by hippocampal neurons. A compartmentalized microfluidic device has been designed to separate axons and dendrites from each other. By applying Qdot-BDNF only to the axon chamber and observing some Qdot-BDNF leaving from the dendrite chamber, it is clearly proved that BDNF up-taken from the axon terminal can be translocated all the way to dendrites. Qdot-BDNF entering and leaving the soma has also been directly observed. Whether BDNF is released from the axon or dendrite terminal is under investigation. It is hoped that at the end of this work, an overall picture of the whole regulation cycle of exogenous BDNF and whether its role as a chemical communicator through the neuronal network can be clearly shown.