MARCKS-dependent mucin clearance and lipid metabolism in ependymal cells are required for maintenance of forebrain homeostasis during aging

Nagendran Muthusamy, Laura J. Sommerville, Adam J. Moeser, Deborah J. Stumpo, Philip Sannes, Kenneth Adler, Perry J. Blackshear, Jill M. Weimer, H. Troy Ghashghaei

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)764-773
Number of pages10
JournalAging Cell
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Aging
  • Barrier function
  • Cerebral cortex
  • Clca3
  • Ependymal cells
  • Lipid droplets
  • Mucin
  • Oxidative stress

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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