Your new experience awaits. Try the new design now and help us make it even better

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 PhamViana Quynh PhamMelike  TutunculerMelike TutunculerHalah  Al DulaimiHalah Al DulaimiDaniel  ArdjmandDaniel ArdjmandWilliam  FleischmannWilliam FleischmannTomas  BachorTomas BachorAllison  XuAllison Xu*
  • University of California, San Francisco, San Francisco, United States

The final, formatted version of the article will be published soon.

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.