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NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 2/2014

01-06-2014 | Original Paper

Neuronal and Astroglial TGFβ-Smad3 Signaling Pathways Differentially Regulate Dendrite Growth and Synaptogenesis

Authors: Chuan-Yong Yu, Wei Gui, Hui-Yan He, Xiao-Shan Wang, Jian Zuo, Lin Huang, Nong Zhou, Kai Wang, Yu Wang

Published in: NeuroMolecular Medicine | Issue 2/2014

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Abstract

To address the role of the transforming growth factor beta (TGFβ)-Smad3 signaling pathway in dendrite growth and associated synaptogenesis, we used small inhibitory RNA to knockdown the Smad3 gene in either cultured neurons and or primary astrocytes. We found that TGFβ1 treatment of primary neurons increased dendrite extensions and the number of synapsin-1-positive synapses. When Smad3 was knockdown in primary neurons, dendrite growth was inhibited and the number of synapsin-1-positive synapses reduced even with TGFβ1 treatment. When astrocyte-conditioned medium (ACM), collected from TGFβ1-treated astrocytes (TGFβ1-stimulated ACM), was added to cultured neurons, dendritic growth was inhibited and the number of synapsin-1-positive puncta reduced. When TGFβ1-stimulated ACM was collected from astrocytes with Smad3 knocked down, this conditioned media promoted the growth of dendrites and the number of synapsin-1-positive puncta in cultured neurons. We further found that TGFβ1 signaling through Smad3 increased the expression of chondroitin sulfate proteoglycans, neurocan, and phosphacan in ACM. Application of chondroitinase ABC to the TGFβ1-stimulated ACM reversed its inhibitory effects on the dendrite growth and the number of synapsin-1-positive puncta. On the other hand, we found that TGFβ1 treatment caused a facilitation of Smad3 phosphorylation and translocation to the nucleus induced by status epilepticus (SE) in wild-type (Smad3+/+) mice, and this treatment also caused a promotion of γ-aminobutyric acid-ergic synaptogenesis impaired by SE in Smad3+/+ as well as in Smad3−/− mice, but more dramatic promotion in Smad3+/+ mice. Thus, we provide evidence for the first time that TGFβ-Smad3 signaling pathways within neuron and astrocyte differentially regulate dendrite growth and synaptogenesis, and this pathway may be involved in the pathogenesis of some central nervous system diseases, such as epilepsy.
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Metadata
Title
Neuronal and Astroglial TGFβ-Smad3 Signaling Pathways Differentially Regulate Dendrite Growth and Synaptogenesis
Authors
Chuan-Yong Yu
Wei Gui
Hui-Yan He
Xiao-Shan Wang
Jian Zuo
Lin Huang
Nong Zhou
Kai Wang
Yu Wang
Publication date
01-06-2014
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 2/2014
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-014-8293-y

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