Age-related changes in regiospecific expression of Lipolysis Stimulated Receptor (LSR) in mice brain.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Aging/*metabolism ; Brain/*metabolism ; Receptors, Lipoprotein/*metabolism; Aging/genetics ; Animals ; Brain/anatomy & histology ; Cholesterol/metabolism ; Homeostasis ; Humans ; Lipolysis ; Male ; Mice ; Mice, Inbred C57BL ; Neuroglia/metabolism ; Neurons/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Lipoprotein/deficiency ; Receptors, Lipoprotein/genetics ; Tissue Distribution ; Transcriptome

The regulation of cholesterol, an essential brain lipid, ensures proper neuronal development and function, as demonstrated by links between perturbations of cholesterol metabolism and neurodegenerative diseases, including Alzheimer's disease. The central nervous system (CNS) acquires cholesterol via de novo synthesis, where glial cells provide cholesterol to neurons. Both lipoproteins and lipoprotein receptors are key elements in this intercellular transport, where the latter recognize, bind and endocytose cholesterol containing glia-produced lipoproteins. CNS lipoprotein receptors are like those in the periphery, among which include the ApoB, E binding lipolysis stimulated lipoprotein receptor (LSR). LSR is a multimeric protein complex that has multiple isoforms including α and α', which are seen as a doublet at 68 kDa, and β at 56 kDa. While complete inactivation of murine lsr gene is embryonic lethal, studies on lsr +/- mice revealed altered brain cholesterol distribution and cognitive functions. In the present study, LSR profiling in different CNS regions revealed regiospecific expression of LSR at both RNA and protein levels. At the RNA level, the hippocampus, hypothalamus, cerebellum, and olfactory bulb, all showed high levels of total lsr compared to whole brain tissues, whereas at the protein level, only the hypothalamus, olfactory bulb, and retina showed the highest levels of total LSR. Interestingly, major regional changes in LSR expression were observed in aged mice which suggests changes in cholesterol homeostasis in specific structures in the aging brain. Immunocytostaining of primary cultures of mature murine neurons and glial cells isolated from different CNS regions showed that LSR is expressed in both neurons and glial cells. However, lsr RNA expression in the cerebellum was predominantly higher in glial cells, which was confirmed by the immunocytostaining profile of cerebellar neurons and glia. Based on this observation, we would propose that LSR in glial cells may play a key role in glia-neuron cross talk, particularly in the feedback control of cholesterol synthesis to avoid cholesterol overload in neurons and to maintain proper functioning of the brain throughout life.
Competing Interests: The authors have declared that no competing interests exist.

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0 (RNA, Messenger)
0 (Receptors, Lipoprotein)
0 (angulin-1 protein, mouse)
97C5T2UQ7J (Cholesterol)

Date Created: 20190625 Date Completed: 20200218 Latest Revision: 20200309

20240104

PMC6590887

10.1371/journal.pone.0218812

31233547