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Updated: May 3, 2026

An Optogenetic Approach for Assessing Formation of Neuronal Connections in a Co-culture System
Published on: February 17, 2015
Differential synaptic signaling responses in human cortical organoids after photon and proton irradiation
Yuting Jiang1, Danieli Born Guerra1, Daniëlle C Voshart1
1Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Abstract:
Brain tumors are the most common solid cancer in children, with radiotherapy being a primary treatment. Proton therapy, with its precise dose distribution, is increasingly being used in these patients to minimize damage to the developing brain. However, the biological effects of proton irradiation on the human brain remain unclear. To investigate this, human cortical organoids were exposed to conventional photons, plateau protons, and spread-out Bragg peak (SOBP) protons, followed by comparative transcriptomic profiling. While photons and protons induced similar transcriptional profiles characterized by apoptosis and downregulation of DNA replication, SOBP protons uniquely downregulated genes involved in brain development and synaptic signaling. Functional calcium imaging, cell deconvolution analysis, and immunostaining indicated that SOBP protons impaired neural network function, due to reduced synaptic density and loss in excitatory neuron progenitors. These findings underscore the distinct biological effects of SOBP protons and their potential impact on the developing brain.
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