Age-dependent changes in lipid droplet distribution and vascularization in naked mole rat vs. mouse hippocampus

The accumulation of lipid droplets in microglia has been reported to increase in response to ageing and age-related diseases like Alzheimer's disease. The present study investigates changes in lipid droplet dynamics with increasing age in the mouse and the similarly sized long-lived rodent, the naked mole rat (Heterocephalus glaber). We show that the naked mole rat contains large amounts of microglial lipid droplets in the CA1 and CA3 region of the hippocampus with an age-dependent increase in the CA3 region. Neuronal lipid droplet size is unaffected by age in the naked mole rat. The mouse hippocampus contains fewer microglial lipid droplets and shows no age-dependent change. However, neuronal lipid droplet size increases with age in the CA3 region in mice. These results could indicate two different ways of regulating lipid accumulation in the brain, where the naked mole rat shuttles their lipids from neurons to microglia to prevent neuronal lipotoxicity and neurodegeneration, while this does not seem to happen in mice. This shuttling of lipids between cells could be a protective mechanism contributing to the high resilience against diseases and damages to the brain seen in the naked mole rat. Additionally, we show that the brain of the naked mole rat has a lower vascularization than the mouse in the dentate hilus, stratum radiatum, and sensory/motor cortex. This could be coupled to the naked mole rats' low metabolism and conforms with its ability to live with low concentrations of oxygen without damage to the brain.