The Role of ApoE in Fatty Acid Transport from Neurons to Astrocytes Under Ischemia/hypoxia Conditions

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2024 Feb 23

PMID 38393618

Authors

Hongyan Chen

Shaozhi Zhao

Qiang Jian

Yinfang Yan

Simin Wang

Xinwen Zhang

Yuqiang Ji

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to investigate whether ischemia/hypoxia conditions induce fatty acid transport from neurons to astrocytes and whether this mechanism is affected by ApoE isoforms.

Methods And Results: A neonatal rat model of hypoxic-ischemic brain damage was established. Excessive accumulation of lipid droplets and upregulation of ApoE expression occurred in the hippocampus and cerebral cortex after hypoxia-ischemia, which implied the occurrence of abnormal fatty acid metabolism. Lipid peroxidation was induced in an oxygen-glucose deprivation and reperfusion (OGDR) model of ApoE primary neurons. The number of BODIPY 558/568 C12-positive particles (fatty acid markers) transferred from neurons to astrocytes was significantly increased with the addition of human recombinant ApoE compared with that in the OGDR group, which significantly increased the efficiency of fatty acid transport from neurons to astrocytes and neuronal viability. However, ApoE4 was found to be associated with lower efficiency in fatty acid transport and less protective effects in OGDR-induced neuronal cell death than both ApoE2 and ApoE3. COG133, an ApoE-mimetic peptide, partially compensated for the adverse effects of ApoE4. FABP5 and SOD1 gene and protein expression levels were upregulated in astrocytes treated with BODIPY 558/568 C12 particles.

Conclusions: In conclusion, ApoE plays an important role in mediating the transport of fatty acids from neurons to astrocytes under ischemia/hypoxia conditions, and this transport mechanism is ApoE isoform dependent. ApoE4 has a low transfer efficiency and may be a potential target for the clinical treatment of neonatal hypoxic-ischemic encephalopathy.

Citing Articles

Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases.

Zhang L, Zhou Y, Yang Z, Jiang L, Yan X, Zhu W J Neuroinflammation. 2025; 22(1):7.

PMID: 39806503 PMC: 11730833. DOI: 10.1186/s12974-025-03334-5.

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