PDF(Pubmed)
Abstract：
Radiation therapy (RT) is a crucial treatment modality for central nervous system (CNS) tumors but toxicity to healthy CNS tissues remains a challenge. Additionally, environmental exposure to radiation during nuclear catastrophes or space travel presents a risk of CNS toxicity. However, the underlying mechanisms of radiation-induced CNS toxicity are not fully understood. Neural progenitor cells (NPCs) are highly radiosensitive, resulting in decreased neurogenesis in the hippocampus. This study aimed to characterize a novel platform utilizing rat NPCs cultured as 3D neurospheres (NSps) to screen the safety and efficacy of experimental drugs with and without radiation exposure. The effect of radiation on NSp growth and differentiation was assessed by measuring sphere volume and the expression of neuronal differentiation markers Nestin and GFAP and proliferation marker Ki67. Radiation exposure inhibited NSp growth, decreased proliferation, and increased GFAP expression, indicating astrocytic differentiation. RNA sequencing analysis supported these findings, showing upregulation of Notch, BMP2/4, S100b, and GFAP gene expression during astrogenesis. By recapitulating radiation-induced toxicity and astrocytic differentiation, this single-NSp culture system provides a high-throughput preclinical model for assessing the effects of various radiation modalities and evaluates the safety and efficacy of potential therapeutic interventions in combination with radiation.
摘要：
放射治疗（RT）是中枢神经系统（CNS）肿瘤的关键治疗方式，但对健康CNS组织的毒性仍然是一个挑战。此外,在核灾难或太空旅行期间，环境暴露于辐射存在中枢神经系统毒性的风险。然而,辐射诱导中枢神经系统毒性的潜在机制尚不完全清楚.神经祖细胞（NPCs）对辐射高度敏感，导致海马神经发生减少。这项研究旨在表征一种新型平台，该平台利用培养为3D神经球（NSps）的大鼠NPC来筛选有和没有辐射暴露的实验药物的安全性和有效性。通过测量球体体积和神经元分化标志物Nestin和GFAP以及增殖标志物Ki67的表达来评估辐射对NSp生长和分化的影响。辐射暴露抑制了NSp的生长，减少增殖，GFAP表达增加，表明星形细胞分化。RNA测序分析支持了这些发现，显示缺口的上调，BMP2/4,S100b,和GFAP基因在星形过程中的表达。通过概括辐射诱导的毒性和星形细胞分化，这种单NSp培养系统提供了一种高通量的临床前模型,用于评估各种放射方式的效果,并评估潜在治疗性干预措施联合放射的安全性和有效性.
