Nutritionally-Induced Plasticity of the Blood-Brain Barrier in Adult Ewes

Presentation Number: LB SAT 57
Date of Presentation: April 1st, 2017

Ligia Dias Prezotto*1, Jennifer Frances Thorson1, Dale A Redmer2 and Anna Grazul-Bilska2
1Montana State University, Havre, MT, 2North Dakota State University, Fargo, ND

Abstract

The blood-brain barrier (BBB) regulates transport of molecules that convey global energetic status to the feeding circuitry within the arcuate nucleus of the hypothalamus (ARC). Ependymal cells, known as tanycytes, are a critical component of the BBB that line the floor and ventrolateral walls of the third ventricle (3V). Tanycyte barrier function is permitted by tight junctions that prevent paracellular diffusion of ions and molecules. However, tanycytes also send cellular projections into the ARC in close proximity to neuronal circuitry that perceive global energetic status. Therefore, tanycytes may play a functional role in neuronal perception of energetic status and homeostasis. We hypothesized that 1) reduced nutritional status would increase the permeability of the BBB through decreased tight junction integrity within the ARC and 2) increased nutritional status would decrease the permeability of the BBB by decreasing tanycyte cellular penetration into the ARC. To study the influence of energetic status on tight junction integrity and tanycyte plasticity, hypothalamic tissue collected from mature ewes offered divergent planes of nutrition were used for immunohistochemistry. Nutritional treatments (n = 4/treatment) were offered at 60 (underfed), 100 (control), or 200 (overfed) % of dietary requirements for 75 days. Zonula occludens-1 (ZO-1) was immunodetected along the ventrolateral wall of the 3V in order to assess tight junction integrity. ZO-1 was distributed in a honeycomb-like shape around tanycyte cellular soma lining the wall of the 3V. However, no differences in tight junction integrity were observed between dietary treatments (P = 0.65). Furthermore, when colocalization rate of ZO-1 and vimentin (tanycyte marker) were assessed between treatments, no differences were observed (P = 0.28). When tanycyte cellular penetration into the ARC was measured, we observed that overfed ewes exhibited longer (P ≤ 0.002) cellular processes when compared to control and underfed ewes, while cellular length did not differ between underfed and control ewes (P = 0.24). Moreover, underfed ewes had greater (P ≤ 0.03) overall tanycyte cellular density than control and overfed ewes. These results indicate that morphological changes occur in tanycyte cells of the ARC as an adaptation to nutrient availability during adult life. These changes seem to occur in an effort to maintain energy homeostasis in response to variations in circulating concentrations of glucose. Therefore, regulating transport of molecules that convey global energetic status of the animal across the BBB to the feeding circuitry within the hypothalamus seems to be an integral and plastic means to maintain homeostasis.

 

Nothing to Disclose: LDP, JFT, DAR, AG