Title

Reactive Oxygen Species Are Involved in BMP-Induced Dendritic Growth in Cultured Rat Sympathetic Neurons

Status

Faculty

School

School of Science

Department

Biology

Document Type

Article

Publication Date

7-2015

Publication Title

Molecular and Cellular Neuroscience

Description/Abstract

Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons.

Keywords

Antioxidants, Bone morphogenetic proteins, DendritesFree radicals, Reactive oxygen species, Sympathetic neurons

Volume

67

First Page

116

Last Page

125

Scholarly

yes

DOI

10.1016/j.mcn.2015.06.007

Disciplines

Biology

Comments

Epub 2015 Jun 14; Charlotte Lea was a Saint Mary’s Student

Original Citation

Vidya Chandrasekaran (Biology): “Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons,” by Vidya Chandrasekaran, Lea C, Sosa JC, Higgins D, in Mol Cell Neurosci. 2015 Jul; 67:116-25; doi: 10.1016/j.mcn.2015.06.007; Epub 2015 Jun 14. https://doi.org/10.1016/j.mcn.2015.06.007

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