Aberrant Choroid Plexus Formation Drives the Development of Treatment-Related Brain Toxicity

Authors

Tamara Bender
Esther Schickel
Celine Schielke
Jürgen Debus
David R Grosshans
Marco Durante
Insa S Schroeder

Publication Date

2-22-2025

Journal

Communications Biology

Abstract

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1+/AQP1+/CLDN3+-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, known to be expressed in CP and cerebrospinal fluid. The altered differentiation is attributed to changes in the WNT/BMP signaling pathways. We conclude that aberrant CP formation can be involved in radiation-induced brain lesions providing additional strategies for possible countermeasures.

Keywords

Choroid Plexus, Animals, Organoids, Mice, Brain Neoplasms, Brain, Humans, Cell Differentiation, Wnt Signaling Pathway

DOI

10.1038/s42003-025-07736-2

PMID

39987290

PMCID

PMC11846864

PubMedCentral® Posted Date

2-22-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes