Hyperglycemia Increases SCO-spondin and Wnt5a Secretion into the Cerebrospinal Fluid to Regulate Ependymal Cell Beating and Glucose Sensing

Overview

Journal PLoS Biol

Specialty Biology

Date 2023 Sep 21

PMID 37733692

Authors

Francisco Nualart

Manuel Cifuentes

Eder Ramirez

Fernando Martinez

Maria Jose Barahona

Luciano Ferrada

Natalia Saldivia

Ernesto R Bongarzone

Bernard Thorens

Katterine Salazar

Affiliations

Soon will be listed here.

Abstract

Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLUT2 decreases hyperglycemia-induced SCO-spondin secretion. In addition, SCO cells secrete Wnt5a-positive vesicles; thus, Wnt5a and SCO-spondin are found at the apex of dorsal ependymal cilia to regulate ciliary beating. Frizzled-2 and ROR2 receptors, as well as specific proteoglycans, such as glypican/testican (essential for the interaction of Wnt5a with its receptors) and Cx43 coupling, were also analyzed in ependymal cells. Finally, we propose that the SCO-spondin/Wnt5a/Frizzled-2/Cx43 axis in ependymal cells regulates ciliary beating, a cyclic and adaptive signaling mechanism to control glucose sensing.

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