Journal Article

GSI-2025-00460

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aberrant choroid plexus formation drives the development of treatment-related brain toxicity

Bender, T. (First author)GSI* ; Schickel, E.GSI* ; Schielke, C.GSI* ; Debus, J. ; Grosshans, D. R. (Corresponding author) ; Durante, M. (Corresponding author)GSI* ; Schröder, I. S. (Corresponding author)GSI*

2025
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s42003-025-07736-2  doi:10.15120/GSI-2025-00460

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.

Keyword(s): Choroid Plexus: metabolism (MeSH) ; Choroid Plexus: radiation effects (MeSH) ; Animals (MeSH) ; Organoids: metabolism (MeSH) ; Mice (MeSH) ; Brain Neoplasms: genetics (MeSH) ; Brain Neoplasms: pathology (MeSH) ; Brain Neoplasms: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Brain: radiation effects (MeSH) ; Brain: pathology (MeSH) ; Humans (MeSH) ; Cell Differentiation (MeSH) ; Wnt Signaling Pathway (MeSH)

Note: This work was funded by US NIH Grant1RO1CA256848-01, and German Federal Ministry of Education andResearch (BMBF) Grant 02 NUK 049A and 02NUK081A. This article is licensed under a Creative Commons Attribution 4.0 International License,

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Contributing Institute(s):

1. Biophysik (BIO)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. SUC-GSI-Heidelberg - Strategic university cooperation GSI-U Heidelberg (SUC-GSI-HE) (SUC-GSI-HE)
3. SUC-GSI-Darmstadt - Strategic university cooperation GSI-TU Darmstadt (SUC-GSI-DA) (SUC-GSI-DA)

Experiment(s):

1. External experiment at external facility/ no experiment at GSI (other)
2. Biophysics experiment at GSI, but no LSRF/no experiment at the GSI accelerator complex (none)

Appears in the scientific report 2025

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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