Effects of cranial X-ray irradiation in Presymptomatic 3 × Tg-AD mice

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-09-23 DOI:10.1016/j.expneurol.2025.115482

Wei Cheng , Yanxi Ma , Feifei Gao , Zheng Shi , Dashan Zuo , Cuixia Di , Xiaodong Jin , Weiqiang Chen , Fei Ye , Qiang Li

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Abstract

Background

Recently, several animal studies have demonstrated the therapeutic potential of low-dose radiation therapy (LDRT) for Alzheimer's disease (AD), especially in decreasing amyloid-beta (Aβ) plaques. However, clinical concerns regarding the duration of efficacy and long-term safety of this treatment remain understudied. Additionally, LDRT has been shown to alleviate various neurological disorders. We hypothesize that the therapeutic mechanisms of LDRT in AD may extend beyond targeting Aβ and tau alone. In this study, we administered whole-brain X-ray irradiation (10 Gy in 5 fractions) to presymptomatic AD mice to re-examine its mechanism of action, duration of efficacy, and long-term safety profile.

Results

Two months after irradiation, the autonomous activity of 3 × Tg-AD mice was significantly enhanced, with specific improvements in the spatial learning and memory in females. Western blotting revealed reduced tau phosphorylation at Ser262 site in the hippocampus of females. SnRNA-seq demonstrated restored neuronal network in females. However, these therapeutic effects appeared exhibited transient characteristics. By ten months post-irradiation, no significant behavioral and AD-related pathological changes were detected across groups, except for the elevated Aβ1–42 in the hippocampus of females.

Conclusions

In conclusion, the effects of early X-ray intervention on 3 × Tg-AD mice were sex-specific and time-dependent. The short-term improvement observed in female mice may be attributed to attenuated tau hyperphosphorylation and restored neuronal networks. Longitudinal observation over ten consecutive months post-irradiation showed no evidence of severe adverse effects.

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颅脑x线照射对症状前3 × Tg-AD小鼠的影响。

背景：最近，一些动物研究已经证明了低剂量放射治疗（LDRT）对阿尔茨海默病（AD）的治疗潜力，特别是在减少淀粉样蛋白- β (Aβ)斑块方面。然而，关于这种治疗的疗效持续时间和长期安全性的临床问题仍未得到充分研究。此外，LDRT已被证明可以缓解各种神经系统疾病。我们假设LDRT治疗AD的机制可能不仅仅针对Aβ和tau。在这项研究中，我们对症状前AD小鼠进行了全脑x射线照射（10 Gy分5次），以重新检查其作用机制、疗效持续时间和长期安全性。结果：照射2个月后，3只 × Tg-AD小鼠的自主活动明显增强，雌性小鼠的空间学习和记忆能力有明显改善。Western blotting显示，雌性海马Ser262位点的tau磷酸化减少。SnRNA-seq显示雌性神经网络恢复。然而，这些治疗效果表现出短暂性。照射后10个月，除雌性海马Aβ1-42升高外，各组均未见明显的行为和ad相关病理改变。结论：早期x线干预对3只 × Tg-AD小鼠的影响具有性别特异性和时间依赖性。在雌性小鼠中观察到的短期改善可能归因于tau过度磷酸化的减弱和神经网络的恢复。辐照后连续10个月的纵向观察未发现严重不良反应的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.