Brain region-specific immunolocalization of the lipolysis-stimulated lipoprotein receptor (LSR) and altered cholesterol distribution in aged LSR+/− mice

Brain lipid homeostasis is important for maintenance of brain cell function and synaptic communications, and is intimately linked to age‐related cognitive decline. Because of the blood–brain barrier's limiting nature, this tissue relies on a complex system for the synthesis and receptor‐mediated uptake of lipids between the different networks of neurons and glial cells. Using immunofluorescence, we describe the region‐specific expression of the lipolysis‐stimulated lipoprotein receptor (LSR), in the mouse hippocampus, cerebellum Purkinje cells, the ependymal cell interface between brain parenchyma and cerebrospinal fluid, and the choroid plexus. Colocalization with cell‐specific markers revealed that LSR was expressed in neurons, but not astrocytes. Latency in arms of the Y‐maze exhibited by young heterozygote LSR+/− mice was significantly different as compared to control LSR+/+, and increased in older LSR+/− mice. Filipin and Nile red staining revealed membrane cholesterol content accumulation accompanied by significantly altered distribution of LSR in the membrane, and decreased intracellular lipid droplets in the cerebellum and hippocampus of old LSR+/− mice, as compared to control littermates as well as young LSR+/− animals. These data therefore suggest a potential role of LSR in brain cholesterol distribution, which is particularly important in preserving neuronal integrity and thereby cognitive functions during aging. Mouse brain expression of the lipolysis‐stimulated lipoprotein receptor (LSR) and its potential role in regulating brain cholesterol homeostasis. Lipid homeostasis plays an important role in maintaining proper brain neuronal function and cognition. LSR is expressed in the neurons of specific brain regions and 18‐month‐old LSR+/− mice demonstrate modified brain cholesterol distribution and decreased latency in the Y‐maze paradigm. These results suggest an important role for this receptor in the regulation of brain cholesterol distribution, which is important in preserving neuronal integrity and thereby cognitive functions during aging.