小胶质细胞的耗竭和重新增殖不会改变颅脑照射对海马神经发生的影响。
Microglia depletion and repopulation do not alter the effects of cranial irradiation on hippocampal neurogenesis.
发表日期:2024 Aug 30
作者:
Kai Zhou, Georgios Alkis Zisiadis, Monique Havermans, Adamantia Fragkopoulou, Cecilia Dominguez, Makiko Ohshima, Ahmed M Osman, Carlos F D Rodrigues, Klas Blomgren
来源:
BRAIN BEHAVIOR AND IMMUNITY
摘要:
颅脑放射治疗可能会导致儿童脑肿瘤幸存者终生认知并发症,而海马神经发生的减少被认为是造成这种情况的原因。辐射(IR)后,小胶质细胞清除死亡的神经祖细胞并产生神经炎症微环境,促进存活祖细胞从神经元分化为神经胶质细胞分化。最近,小胶质细胞的消耗和重新增殖被证明可以促进各种脑损伤模型中的神经发生并改善认知缺陷。在这项研究中,我们利用 Cx3cr1CreERt2-YFP/Rosa26DTA/转基因小鼠模型来消耗幼年小鼠大脑中的小胶质细胞,然后对它们进行全脑 IR,并研究对海马神经发生的短期和长期影响。在 IR 后的最初 24 小时内,小胶质细胞的缺失导致颗粒下区死细胞的积累,趋化因子 C-C 基序配体 2 (CCL2) 的水平高出 50 倍,而假脑中的趋化因子 C-C 基序配体 2 (CCL2) 水平高出 7 倍红外后。小胶质细胞的缺失以及随后 10 天内的重新增殖,既不影响增殖细胞或双皮质素阳性细胞的损失,也不影响颗粒细胞层生长的减少。我们的结果反对促炎症微环境在海马神经发生失调中的作用,并表明观察到的神经发生减少完全是由于 IR。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
Cranial radiotherapy can cause lifelong cognitive complications in childhood brain tumor survivors, and reduced hippocampal neurogenesis is hypothesized to contribute to this. Following irradiation (IR), microglia clear dead neural progenitors and give rise to a neuroinflammatory microenvironment, which promotes a switch in surviving progenitors from neuronal to glial differentiation. Recently, depletion and repopulation of microglia were shown to promote neurogenesis and ameliorate cognitive deficits in various brain injury models. In this study, we utilized the Cx3cr1CreERt2-YFP/+Rosa26DTA/+ transgenic mouse model to deplete microglia in the juvenile mouse brain before subjecting them to whole-brain IR and investigated the short- and long-term effects on hippocampal neurogenesis. Within the initial 24 h after IR, the absence of microglia led to an accumulation of dead cells in the subgranular zone, and 50-fold higher levels of the chemokine C-C motif ligand 2 (CCL2), in sham brains and 7-fold higher levels after IR. The absence of microglia, and the subsequent repopulation within 10 days, did neither affect the loss of proliferating or doublecortin-positive cells, nor the reduced growth of the granule cell layer. Our results argue against a role for a pro-inflammatory microenvironment in the dysregulation of hippocampal neurogenesis and suggest that the observed reduction of neurogenesis was solely due to IR.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.