BRIEF RESEARCH REPORT article
Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1634283
Modulation of fenestrated vasculature in the median eminence and area postrema in response to neurotoxin exposure and its impairment in aging
Provisionally accepted
Viana Quynh Pham
Melike TutunculerHalah Al DulaimiDaniel ArdjmandWilliam FleischmannTomas Bachor
Allison Xu*- University of California, San Francisco, San Francisco, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Effective communication between the brain and peripheral tissues is crucial for homeostasis and health, and its impairment is a defining feature of aging. Circumventricular organs, characterized by the presence of fenestrated capillaries and absence of a blood-brain barrier (BBB), play a crucial role in controlling substance exchange between the brain and the blood. To date, adaptive changes in fenestrated vasculature in response to environmental insults remain poorly understood. In this study, we show that fenestrated capillaries in the median eminence (ME) and area postrema (AP)-two distinct circumventricular organs critical for metabolic controlundergo differential remodeling when exposed to circulating monosodium glutamate (MSG), a BBB-impermeable neurotoxin. Upon MSG exposure, fenestrated capillaries and vascular permeability were decreased in the ME but increased in the AP, and these changes were closely associated with the expression of angiogenic factors pleiotrophin (Ptn) and vascular endothelial growth factor A (Vegfa). In both ME and AP, adult tanycytes expressed high levels of Ptn and have processes in close contact with fenestrated capillaries. Significantly, the adaptive regulation of Ptn expression and the ability to modulate fenestrated capillaries and vascular permeability were abolished in both ME and AP of aged animals. Together, our findings suggest that tanycytic expressions of the angiogenic factor PTN, in conjunction with VEGF, are differentially regulated in distinct circumventricular organs upon exposure to neurotoxins, leading to regionspecific remodeling of fenestrated endothelium. Our study further demonstrates that the loss of plasticity in fenestrated vasculature may be a hallmark feature of brain aging.
Keywords: Fenestrated capillaries, circumventricular organs, Median Eminence, Area Postrema, Aging, tanycytes, PTN, VEGF
Received: 24 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Pham, Tutunculer, Al Dulaimi, Ardjmand, Fleischmann, Bachor and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Allison Xu, University of California, San Francisco, San Francisco, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.