Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus

Frías-Anaya, E. and Gromnicova, R. and Kraev, I. and Rogachevsky, V. and Male, D.K. and Crea, F. and Hawkes, C.A. and Romero, I.A. (2021) Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus. Neurobiology of Aging, 101. pp. 273-284. ISSN 0197-4580

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Blood-brain barrier (BBB) breakdown occurs in aging and neurodegenerative diseases. Although age-associated alterations have previously been described, most studies focused in male brains; hence, little is known about BBB breakdown in females. This study measured ultrastructural features in the aging female BBB using transmission electron microscopy and 3-dimensional reconstruction of cortical and hippocampal capillaries from 6- and 24-month-old female C57BL/6J mice. Aged cortical capillaries showed more changes than hippocampal capillaries. Specifically, the aged cortex showed thicker basement membrane, higher number and volume of endothelial pseudopods, decreased endothelial mitochondrial number, larger pericyte mitochondria, higher pericyte–endothelial cell contact, and increased tight junction tortuosity compared with young animals. Only increased basement membrane thickness and pericyte mitochondrial volume were observed in the aged hippocampus. Regional comparison revealed significant differences in endothelial pseudopods and tight junctions between the cortex and hippocampus of 24-month-old mice. Therefore, the aging female BBB shows region-specific ultrastructural alterations that may lead to oxidative stress and abnormal capillary blood flow and barrier stability, potentially contributing to cerebrovascular diseases, particularly in postmenopausal women.

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Journal Article
Journal or Publication Title:
Neurobiology of Aging
Additional Information:
This is the author’s version of a work that was accepted for publication in Neurobiology of Aging. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neurobiology of Aging, 101, 2021 DOI: 10.1016/j.neurobiolaging.2020.12.008
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08 Mar 2021 13:55
Last Modified:
19 Sep 2023 02:35