THE EFFECTS OF DIFFERENT DIETARY CONDITIONS ON THE ULTRASTRUCTURE OF FENESTRATED ENDOTHELIAL CELLS IN THE MEDIAN EMINENCE

The median eminence (ME) is a circumventricular organ located next to the arcuate nucleus, characterized by fenestrated endothelial cells. It is crucial for exchange of hormones, nutrients, and other factors between the blood and brain. Fenestrated endothelial cells in the ME undergo dynamic remodelling in response to dietary changes, such as fasting and high fat diets. However, it is unknown whether dietary protein restriction also modulates fenestration expression. We aim to understand dynamic remodelling of endothelial cell fenestrations (ultrastructure) in the ME in response to different dietary conditions.
Visualizing fenestrations is challenging as they are smaller than light’s diffraction limit. As such, immunohistochemistry cannot resolve key characteristics of fenestrations, such as size and number. Therefore, we developed a protocol for scanning electron microscopy to directly visualize fenestrations in the ME of the mouse brain.
We show that ME capillaries are highly fenestrated, with fenestrations that are smaller than those observed in other tissues (30-100 nm, mean size 55 nm). Importantly, no fenestrations were found outside of the ME. We also observed that fenestrations were diaphragmed, consistent with fenestrations in some other tissues (e.g. kidney). Ongoing experiments are comparing characteristics of fenestrations in the ME of mice subjected to different dietary conditions, namely fasting and diets containing different amounts of protein (5% vs. 20%).
Together, this work will further our understanding of the complex remodelling of fenestrated endothelial cells in the brain in response to different nutritional states.