Abstract
Better survival rates among pediatric brain tumor patients have resulted in an increased awareness of late side effects that commonly appear following cancer treatment. Radiation-induced changes in hippocampus and white matter are well described, but do not explain the full range of neurological late effects in childhood cancer survivors. The aim of this study was to investigate thalamus following cranial irradiation (CIR) to the developing brain. At postnatal day 14, male mice pups received a single dose of 8 Gy CIR. Cellular effects in thalamus were assessed using immunohistochemistry 4 months after CIR. Interestingly, the density of neurons decreased with 35% (p = 0.0431) and the density of astrocytes increased with 44% (p = 0.011). To investigate thalamic astrocytes, S100β+ cells were isolated by fluorescence-activated cell sorting and genetically profiled using next-generation sequencing. The phenotypical characterization indicated a disrupted function, such as downregulated microtubules’ function, higher metabolic activity, immature phenotype and degraded ECM. The current study provides novel insight into that thalamus, just like hippocampus and white matter, is severely affected by CIR. This knowledge is of importance to understand the late effects seen in pediatric brain tumor survivors and can be used to give them the best suitable care.
Highlights
Better survival rates among pediatric brain tumor patients have resulted in an increased awareness of the late side effects that can appear following cancer treatment
The main findings from this study were the following: 1) The density of neurons were decreased in the thalamus after cranial irradiation (CIR). 2) The amount of astrocytes were increased in the thalamus following CIR. 3) The phenotype of the astrocytes are affected by CIR, with alterations such as downregulated microtubules’ function, higher metabolic activity, immature phenotype and degraded extracellular matrix (ECM), indicating a disrupted function
A similar cellular effect following cranial radiation has been shown in the hippocampus, where inflammation has been suggested as the driving force in making precursor cells become astrocytes instead of neurons[35]
Summary
Better survival rates among pediatric brain tumor patients have resulted in an increased awareness of the late side effects that can appear following cancer treatment. Cellular effects in the thalamus was first assessed by stereological quantifications of neurons, microglia, oligodendrocytes and astrocytes These analyses revealed a decreased density of neurons and an increased density of astrocytes in the thalamus following CIR. To further unravel the role of this increased proportion of astrocytes, S100 calcium-binding protein (S100β)+ astrocytes were isolated from the thalamus by fluorescence-activated cell sorting (FACS) and genetically profiled using next-generation sequencing (NGS). This phenotypical characterization indicated that thalamic astrocytes are affected by CIR with a disrupted function, such as downregulated microtubules’ function, higher metabolic activity, immature phenotype and degraded ECM. This study provides novel insight into that the thalamus, just like the hippocampus and white matter, is severely affected by CIR
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
