DOI: 10.1101/518787Jan 11, 2019Paper

BDNF/TrkB.T1 signaling is a novel mechanism for astrocyte morphological maturation

BioRxiv : the Preprint Server for Biology
Leanne M HoltMichelle L Olsen

Abstract

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 BDNFs 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.

Related Concepts

Astrocytes
Brain
Gene Deletion
Genes
Growth Factor
Nerve Growth Factors
Neurons
Synapses
Brain-Derived Neurotrophic Factor
Branching (Qualifier Value)

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