TY  - JOUR
AU  - Bender, Tamara
AU  - Schickel, Esther
AU  - Schielke, Celine
AU  - Debus, Jürgen
AU  - Grosshans, David R.
AU  - Durante, Marco
AU  - Schröder, Insa Sigrid
TI  - Aberrant choroid plexus formation drives the development of treatment-related brain toxicity
JO  - Communications biology
VL  - 8
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - GSI-2025-00460
SP  - 276
PY  - 2025
N1  - 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,
AB  - 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.
KW  - Choroid Plexus: metabolism
KW  - Choroid Plexus: radiation effects
KW  - Animals
KW  - Organoids: metabolism
KW  - Mice
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: pathology
KW  - Brain Neoplasms: metabolism
KW  - Brain: metabolism
KW  - Brain: radiation effects
KW  - Brain: pathology
KW  - Humans
KW  - Cell Differentiation
KW  - Wnt Signaling Pathway
LB  - PUB:(DE-HGF)16
C6  - pmid:39987290
UR  - <Go to ISI:>//WOS:001446985200013
DO  - DOI:10.1038/s42003-025-07736-2
UR  - https://repository.gsi.de/record/357806
ER  -