MARCKS ‐dependent mucin clearance and lipid metabolism in ependymal cells are required for maintenance of forebrain homeostasis during aging
| Autor: | Perry J. Blackshear, Adam J. Moeser, H. Troy Ghashghaei, Nagendran Muthusamy, Kenneth B. Adler, Deborah J. Stumpo, Laura J. Sommerville, Philip L. Sannes, Jill M. Weimer |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Aging
medicine.medical_specialty Ependymal Cell lipid droplets Biology Mice Prosencephalon Clca3 mucin Ependyma Internal medicine Lipid droplet medicine Animals Homeostasis Aging brain MARCKS Myristoylated Alanine-Rich C Kinase Substrate Protein kinase C Barrier function Microglia Intracellular Signaling Peptides and Proteins Mucins ependymal cells Membrane Proteins Original Articles Cell Biology Lipid Metabolism Oxidative Stress medicine.anatomical_structure Endocrinology Forebrain cerebral cortex barrier function |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| DOI: | 10.1111/acel.12354 |
| Popis: | Ependymal cells (ECs) form a barrier responsible for selective movement of fluids and molecules between the cerebrospinal fluid and the central nervous system. Here, we demonstrate that metabolic and barrier functions in ECs decline significantly during aging in mice. The longevity of these functions in part requires the expression of the myristoylated alanine-rich protein kinase C substrate (MARCKS). Both the expression levels and subcellular localization of MARCKS in ECs are markedly transformed during aging. Conditional deletion of MARCKS in ECs induces intracellular accumulation of mucins, elevated oxidative stress, and lipid droplet buildup. These alterations are concomitant with precocious disruption of ependymal barrier function, which results in the elevation of reactive astrocytes, microglia, and macrophages in the interstitial brain tissue of young mutant mice. Interestingly, similar alterations are observed during normal aging in ECs and the forebrain interstitium. Our findings constitute a conceptually new paradigm in the potential role of ECs in the initiation of various conditions and diseases in the aging brain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |