In:
Aging Cell, Wiley, Vol. 14, No. 5 ( 2015-10), p. 764-773
Abstract:
Ependymal cells ( EC s) 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 EC s 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 EC s are markedly transformed during aging. Conditional deletion of MARCKS in EC s 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 EC s and the forebrain interstitium. Our findings constitute a conceptually new paradigm in the potential role of EC s in the initiation of various conditions and diseases in the aging brain.
Type of Medium:
Online Resource
ISSN:
1474-9718
,
1474-9726
DOI:
10.1111/acel.2015.14.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2099130-7
SSG:
12