PT  - JOURNAL ARTICLE
AU  - Markus A. Stahlberg
AU  - Sebastian Kügler
AU  - Camin Dean
TI  - Visualizing BDNF cell-to-cell transfer reveals astrocytes are the primary recipient of neuronal BDNF
AID  - 10.1101/255935
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 255935
4099  - http://biorxiv.org/content/early/2018/03/08/255935.short
4100  - http://biorxiv.org/content/early/2018/03/08/255935.full
AB  - Brain-derived neurotrophic factor (BDNF) is essential for neuronal growth, differentiation, and synaptic plasticity. Although the release and effects of BDNF have been well-studied separately, the transfer of BDNF between cells has not been investigated. Using a four-fluorophore imaging approach to identify both the cell of origin and target cells, we quantified the transfer of BDNF. Surprisingly, we found that astrocytes are the main recipient of neuronally expressed BDNF. We further found that astrocytes specifically take up mature (not pro) BDNF released by neurons. Over-expression of TrkB in neurons redirects released BDNF from astrocytes to neurons, indicating that TrkB levels determine neuronal versus astrocytic BDNF uptake. Increased neuronal activity further increased astrocytic (but not neuronal) uptake of neuronally expressed BDNF. Finally, we demonstrate that astrocytes are not simply a sink for excess BDNF, but that BDNF taken up by astrocytes mediates physiological effects on the astrocytic population by increasing astrocytic territory.