Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain

Aging Cell

Brett A. Shook¹  Jessica B. Lennington¹  Rebecca L. Acabchuk¹  Meredith Halling¹  Ye Sun¹  John Peters¹  Qian Wu⁴  Amit Mahajan³  Douglas W. Fellows² 

[1] Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-3156, USA;Department of Diagnostic Imaging and Therapeutics, University of Connecticut Health Center, CT 06030, USA;Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT 06520-8042, USA;Department of Anatomic Pathology and Laboratory Medicine, University of Connecticut Health Center, CT 06030, USA

关键词: aging;    ependymal cells;    human;    injury;    lateral ventricle;    mouse;    neural stem cells;    ventriculomegaly;   

DOI  :  10.1111/acel.12184

来源: Wiley

【 摘 要 】

Summary

Age-associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricle surface gliosis is associated with ventriculomegaly. To examine whether loss of ependymal cell coverage resulting in ventricle surface glial scarring can lead directly to ventricle enlargement independent of any other injury or degenerative loss, we modeled in mice the glial scarring found along the lateral ventricle surface in aged humans. Neuraminidase, which cleaves glycosidic linkages of apical adherens junction proteins, was administered intracerebroventricularly to denude areas of ependymal cells. Substantial ependymal cell loss resulted in reactive gliosis rather than stem cell-mediated regenerative repair of the ventricle lining, and the gliotic regions showed morphologic and phenotypic characteristics similar to those found in aged humans. Increased levels of aquaporin-4, indicative of edema, observed in regions of periventricular gliosis in human tissue were also replicated in our mouse model. 3D modeling together with volume measurements revealed that mice with ventricle surface scarring developed expanded ventricles, independent of neurodegeneration. Through a comprehensive, comparative analysis of the lateral ventricles and associated periventricular tissue in aged humans and mouse, followed by modeling of surface gliosis in mice, we have demonstrated a direct link between lateral ventricle surface gliosis and ventricle enlargement. These studies highlight the importance of maintaining an intact ependymal cell lining throughout aging.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.