Clonidine prevents radiation-induced cell death in human brain organoids

Radiotherapy is a standard treatment of pediatric brain tumors. Though the survival rate has improved for many tumor types, most patients suffer long-term cognitive decline and there is currently no way of preventing radiation-induced damage to healthy brain tissue. Here, we used a human forebrain organoid model to investigate if the α<sub>2</sub>-adrenoceptor and I<sub>1</sub>-imidazoline receptor agonist clonidine could prevent radiotoxicity. We found that treatment of organoids with clonidine significantly reduced radiation-induced loss of neural progenitor cells, neurons, astrocytes, and oligodendrocyte lineage cells. Moreover, clonidine reduced overall DNA damage and signs of reactive gliosis in organoids. Our findings demonstrate that pharmacological rescue of radiation neurotoxicity is possible in a human brain organoid model and provides a rationale for future drug repurposing studies aiming to prevent radiation-induced brain injury in children treated with radiotherapy.

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Journal
Scientific Reports
Published
2025-10-31
DOI
https://doi.org/10.1038/s41598-025-26170-2
Primary Topic
Cancer, Stress, Anesthesia, and Immune Response
Type
article
Field-Weighted Citation Impact
0.00

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article

Clonidine prevents radiation-induced cell death in human brain organoids

Mahnaz Nikpour, Erik Smedler, Marja Koskuvi, Samudyata Samudyata et al.
Scientific Reports
Cancer, Stress, Anesthesia, and Immune Response
article

Clonidine prevents radiation-induced cell death in human brain organoids

Mahnaz Nikpour, Erik Smedler, Marja Koskuvi, Samudyata Samudyata, Bo Stenerlöw, Martin Lundberg, Martin Schalling, Per‐Arne Lönnqvist, Carl M. Sellgren, Asimenia Gkogka, Melis Çelik
article en

Abstract

Radiotherapy is a standard treatment of pediatric brain tumors. Though the survival rate has improved for many tumor types, most patients suffer long-term cognitive decline and there is currently no way of preventing radiation-induced damage to healthy brain tissue. Here, we used a human forebrain organoid model to investigate if the α<sub>2</sub>-adrenoceptor and I<sub>1</sub>-imidazoline receptor agonist clonidine could prevent radiotoxicity. We found that treatment of organoids with clonidine significantly reduced radiation-induced loss of neural progenitor cells, neurons, astrocytes, and oligodendrocyte lineage cells. Moreover, clonidine reduced overall DNA damage and signs of reactive gliosis in organoids. Our findings demonstrate that pharmacological rescue of radiation neurotoxicity is possible in a human brain organoid model and provides a rationale for future drug repurposing studies aiming to prevent radiation-induced brain injury in children treated with radiotherapy.

Scientific ReportsVol. 15(1)
Uppsala University (SE), Karolinska University Hospital (SE), Sahlgrenska University Hospital (SE), Stockholm County Council (SE), Karolinska Institutet (SE), University of Gothenburg (SE)
Familjen Erling-Perssons Stiftelse, Australian Government, One Mind, Svenska Sällskapet för Medicinsk Forskning, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Göteborgs Universitet, Wallenberg Centre for Molecular and Translational Medicine
Openalex Percentile: Top 62%
Cancer, Stress, Anesthesia, and Immune Response
DOIOpen Access PDFOpenAlex
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