Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling

Zhenhua Ren; Xin Wang; Fanmuyi Yang; Mei Xu; Jacqueline A Frank; Haiping Wang; Siying Wang; Zun-Ji Ke; Jia Luo

doi:10.1016/j.bbadis.2017.07.035

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Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling

Journal article

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Peer reviewed

Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling

Zhenhua Ren, Xin Wang, Fanmuyi Yang, Mei Xu, Jacqueline A Frank, Haiping Wang, Siying Wang, Zun-Ji Ke and Jia Luo

Biochimica et biophysica acta. Molecular basis of disease, Vol.1863(11), pp.2746-2761

11/2017

DOI: 10.1016/j.bbadis.2017.07.035

PMID: 28778590

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Abstract

Ethanol exposure during development causes fetal alcohol spectrum disorders (FASD). A large body of evidence shows that ethanol produces multiple abnormalities in the developing central nervous system (CNS), such as smaller brain size, reduced volume of cerebral white matter, permanent loss of neurons, and alterations in synaptogenesis and myelinogenesis. The effects of ethanol on the developing spinal cord, however, receive little attention and remain unclear. We used a third trimester equivalent mouse model to investigate the effect of ethanol on the developing spinal cord. Ethanol caused apoptosis and neurodegeneration in the dorsal horn neurons of mice of early postnatal days, which was accompanied by glial activation, macrophage infiltration, and increased expression of CCR2, a receptor for monocyte chemoattractant protein 1 (MCP-1). Ethanol-induced neuronal death during development resulted in permanent loss of spinal cord neurons in adult mice. Ethanol stimulated endoplasmic reticulum (ER) stress and oxidative stress, and activated glycogen synthase kinase 3β (GSK3β) and c-Jun N-terminal kinase (JNK) pathways. Knocking out MCP-1 or CCR2 made mice resistant to ethanol-induced apoptosis, ER stress, glial activation, and activation of GSK3β and JNK. CCR2 knock out offered much better protection against ethanol-induced damage to the spinal cord. Thus, developmental ethanol exposure caused permanent loss of spinal cord neurons and CCR2 signaling played an important role in ethanol neurotoxicity.

Development

Alcohol

Inflammation

Neurodegeneration

Apoptosis

Details

Title: Subtitle: Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling
Creators: Zhenhua Ren - University of Kentucky
Xin Wang - University of Kentucky
Fanmuyi Yang - University of Kentucky
Mei Xu - University of Kentucky
Jacqueline A Frank - University of Kentucky
Haiping Wang - University of Kentucky
Siying Wang - University of Kentucky
Zun-Ji Ke - Shanghai University of Traditional Chinese Medicine
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: Biochimica et biophysica acta. Molecular basis of disease, Vol.1863(11), pp.2746-2761
DOI: 10.1016/j.bbadis.2017.07.035
PMID: 28778590
NLM abbreviation: Biochim Biophys Acta Mol Basis Dis
ISSN: 0925-4439
eISSN: 1879-260X
Grant note: AA017226 / NIH HHS AA015407 / NIH HHS
Language: English
Date published: 11/2017
Academic Unit: Pathology
Record Identifier: 9984201248202771

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