title: Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.
abstract: We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.
authors.affiliation: Laboratory of Immunophysiology, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: Marilia Kimie
authors.initials: MK
authors.lastname: Shimabukuro
authors.affiliation: Laboratory of Immunophysiology, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: Larissa Gutman Paranhos
authors.initials: LG
authors.lastname: Langhi
authors.affiliation: Laboratory of Cellular Proliferation and Differentiation, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cordeiro
authors.affiliation: Laboratory of Cellular Proliferation and Differentiation, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: José M
authors.initials: JM
authors.lastname: Brito
authors.affiliation: Laboratory of Immunophysiology, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: Claudia Maria de Castro
authors.initials: CM
authors.lastname: Batista
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA, 21224-6825.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Laboratory of Immunophysiology, Institute of Biomedical Sciences, Health Sciences Center, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, Rio de Janeiro, RJ, Brazil, 21941-902.
authors.forename: Valeria de
authors.initials: Vd
authors.lastname: Mello Coelho
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure*; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D066292:Lipid Droplets / Q000378:metabolism / Q000648:ultrastructure*; D008578:Meninges / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000648:ultrastructure*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D000070778:Perilipin-1 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C480860:Map1lc3b protein, mouse; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D000070778:Perilipin-1; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; D014409:Tumor Necrosis Factor-alpha; C528900:glial fibrillary astrocytic protein, mouse; D001616:beta-Galactosidase