RT Journal Article
SR Electronic
T1 BDNF/TrkB.T1 signaling is a novel mechanism for astrocyte morphological maturation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 518787
DO 10.1101/518787
A1 Leanne M. Holt
A1 Natasha L. Pacheco
A1 Raymundo Hernandez
A1 Muhannah Hossain
A1 Michelle L. Olsen
YR 2019
UL http://biorxiv.org/content/early/2019/01/11/518787.abstract
AB Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of neurons, including neuronal morphology and synapse refinement. Herein, we demonstrate astrocytes express high levels of BDNF’s receptor, TrkB (in the top 20 of protein-coding transcripts), with nearly exclusive expression of the truncated isoform, TrkB.T1 which peaks in expression during astrocyte morphological maturation. Using a novel culture paradigm, we show that astrocyte morphological complexity is increased in the presence of BDNF and is dependent upon BDNF/TrkB.T1 signaling. Deletion of TrkB.T1 in vivo revealed morphologically immature astrocytes with significantly reduced volume and branching, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte functions, including synaptogenic genes. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development.