The coupling of neuron-astrocyte lipid metabolism induced by neonatal hypoxic-ischaemic brain damage is ApoE dependent

Abstract

Abstract The aim of this study was to investigate whether neonatal hypoxic-ischaemic brain damage induces lipid metabolism coupling between neurons and astrocytes and whether this mechanism is affected by ApoE isoforms. A neonatal rat model of hypoxic-ischaemic brain damage was established. Excessive accumulation of lipid droplets and upregulation of ApoE expression occurred in the hippocampus and cerebral cortex after ischaemia and hypoxia. In this glucose and oxygen deprivation (OGD) model of ApoE−/− primary neurons, compared with the addition of human recombinant ApoE2 and ApoE3 proteins, the ApoE4 protein significantly reduced neuronal cell viability and the efficiency of lipid transport from neurons to astrocytes after OGD. Notably, the ApoE mimic peptide COG133 could compensate for the harmful effects of ApoE4. In conclusion, lipid metabolism coupling between neurons and astrocytes occurs and is the key to protecting neurons from stress injury after hypoxia-ischaemia; however, ApoE4, as a negative factor, plays a detrimental role in regulating the fatty acid metabolism of neurons and astrocytes and may be a potential target for the clinical treatment of neonatal hypoxic-ischaemic encephalopathy.