Effect of retinoic acid on delayed encephalopathy after acute carbon monoxide poisoning: Role of the lncRNA SNHG15/LINGO-1/BDNF/TrkB axis.
10.11817/j.issn.1672-7347.2025.240318
- Author:
Fangling HUANG
1
,
2
;
Su'e WANG
3
;
Zhengrong PENG
1
,
4
,
5
;
Xu HUANG
6
;
Sufen BAI
6
Author Information
1. Department of Hyperbaric Oxygen, Jiangxi Hospital (National Regional Center for Neurological Diseases), Xiangya Hospital, Central South University, Nanchang
2. hfl915@csu.edu.cn.
3. Department of Preventive Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
4. 13873151139@
5. com.
6. Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha
- Publication Type:Journal Article
- Keywords:
LINGO-1;
apoptosis;
delayed encephalopathy after acute carbon monoxide poisoning;
lncRNA SNHG15;
neuroprotection;
retinoic acid
- MeSH:
Animals;
RNA, Long Noncoding/physiology*;
Brain-Derived Neurotrophic Factor/genetics*;
Carbon Monoxide Poisoning/complications*;
Mice;
Tretinoin/pharmacology*;
Nerve Tissue Proteins/metabolism*;
Membrane Proteins/metabolism*;
Apoptosis/drug effects*;
Hippocampus/cytology*;
Receptor, trkB/metabolism*;
Neurons/drug effects*;
Male;
Brain Diseases/etiology*;
Oligodendroglia/drug effects*;
Signal Transduction;
Cell Line
- From:
Journal of Central South University(Medical Sciences)
2025;50(6):955-969
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:The neurotoxicity of carbon monoxide (CO) to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Our previous study found that retinoic acid (RA) can suppress the neurotoxic effects of CO. This study further explores, in vivo and in vitro, the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.
METHODS:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO, and a DEACMP animal model was established in adult Kunming mice. Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin V/propidium iodide (PI) double staining. The transcriptional and protein expression of each gene was detected using real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Long noncoding RNA (lncRNA) SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes. In DEACMP mice, SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.
RESULTS:RA at 10 and 20 μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes, downregulation of SNHG15 and LINGO-1, and upregulation of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) (all P<0.05). Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity (all P<0.05). Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels (all P<0.05). Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP (all P<0.05).
CONCLUSIONS:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes, thereby reducing central nervous system injury and exerting neuroprotective effects. LncRNA SNHG15 and LINGO-1 are key molecules mediating RA-induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway. These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
