Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord

Zhenhua Ren; Xin Wang; Mei Xu; Jacqueline A Frank; Jia Luo

doi:10.1016/j.alcohol.2018.12.002

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Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord

Journal article

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Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord

Zhenhua Ren, Xin Wang, Mei Xu, Jacqueline A Frank and Jia Luo

Alcohol (Fayetteville, N.Y.), Vol.79, pp.25-35

09/2019

DOI: 10.1016/j.alcohol.2018.12.002

PMID: 30529756

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https://www.ncbi.nlm.nih.gov/pmc/articles/6555701View

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Abstract

Developmental exposure to ethanol may cause fetal alcohol spectrum disorders (FASD), and the immature central nervous system (CNS) is particularly vulnerable to ethanol. In addition to vulnerability in the developing brain, we previously showed that ethanol also caused neuroapoptosis, microglial activation, and neuroinflammation in the spinal cord. Minocycline is an antibiotic that inhibits microglial activation and alleviates neuroinflammation. We sought to determine whether minocycline could protect spinal cord neurons against ethanol-induced damage. In this study, we showed that minocycline significantly inhibited ethanol-induced caspase-3 activation, microglial activation, and the expression of pro-inflammatory cytokines in the developing spinal cord. Moreover, minocycline blocked ethanol-induced activation of glycogen synthase kinase 3 beta (GSK3β), a key regulator of microglial activation. Meanwhile, minocycline significantly restored ethanol-induced inhibition of protein kinase B (AKT), mammalian target of the rapamycin (mTOR), and ERK1/2 signaling pathways, which were important pro-survival signaling pathways for neurons. Together, minocycline may attenuate ethanol-induced damage to the developing spinal cord by inhibiting microglial activation/neuroinflammation and by restoring the pro-survival signaling. •Minocycline protected the developing spinal cord against ethanol-induced damage.•Minocycline inhibited ethanol-induced microglia activation.•Minocycline blocked ethanol-induced activation of GSK3β.•Minocycline reversed ethanol inhibition of pro-survival signaling.

Inflammation

Alcohol

Fetal alcohol spectrum disorders

Glycogen synthase kinase 3

Neuroprotection

Details

Title: Subtitle: Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord
Creators: Zhenhua Ren - University of Kentucky
Xin Wang - University of Kentucky
Mei Xu - University of Kentucky
Jacqueline A Frank - University of Kentucky
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: Alcohol (Fayetteville, N.Y.), Vol.79, pp.25-35
DOI: 10.1016/j.alcohol.2018.12.002
PMID: 30529756
NLM abbreviation: Alcohol
ISSN: 0741-8329
eISSN: 1873-6823
Publisher: Elsevier
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health (NIH), award: AA017226, AA015407; DOI: 10.13039/100000738, name: Department of Veterans Affairs; DOI: 10.13039/100007217, name: Veterans Health Administration; DOI: 10.13039/100006379, name: Office of Research and Development; DOI: 10.13039/100007496, name: Biomedical Laboratory Research and Development, award: BX001721; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 81372693
Language: English
Date published: 09/2019
Academic Unit: Pathology
Record Identifier: 9984186507402771

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