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铁诱导神经炎症的斑马鱼模型的建立

Development of Zebrafish model for Iron Induced Neuroinflammation.

作者信息

Bagwe Parab Siddhi, Kaur Ginpreet

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Mumbai, 56, India.

Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, 56, India.

出版信息

Fish Physiol Biochem. 2025 Sep 8;51(5):160. doi: 10.1007/s10695-025-01575-y.

DOI:10.1007/s10695-025-01575-y
PMID:40920220
Abstract

Zebrafish models have been used to research Alzheimer's disease and other neurodegenerative disorders because of their similarities to the human genetic composition and behavior. Researchers have detected iron accumulation in the post-mortem brain sections of neurodegenerative disorder patients. Therefore, the development an animal model to simulate these clinical pathological findings is important. Iron is an important metal for maintaining homeostasis in the brain, depletion and accumulation of iron hamper neuronal development. Given the importance of iron overload in cognition impairment, this research aimed to develop an iron-induced zebrafish model of cognitive impairment. Zebrafish were subjected to ferrous sulfate (1.5 mg/L, 3 mg/L, and 6 mg/L) for 28 days. The behavioral parameters (Y-maze, novel tank test), oxidative stress parameters (MDA, GSH, and catalase), acetylcholinesterase (AChE) levels, iron levels, and interleukin-1β (IL-1β) levels in brain homogenate were assessed. The behavioral and locomotor responses, specifically in the zebrafish treated with iron for 28 days, suggest an increase in the loss of spatial memory and anxiety. Reactive oxygen species in the brain significantly increased (p < 0.001) with the increase in concentrations of iron. Brain tissue iron content and IL-1β significantly increased (p < 0.001) in the brain homogenate of the zebrafish. This model will aid in the screening of therapeutic compounds to accelerate drug discovery in the field of neurodegenerative diseases.

摘要

由于斑马鱼的基因组成和行为与人类相似,因此已被用于研究阿尔茨海默病和其他神经退行性疾病。研究人员在神经退行性疾病患者的死后脑切片中检测到铁积累。因此,开发一种动物模型来模拟这些临床病理发现很重要。铁是维持大脑内稳态的重要金属,铁的消耗和积累会阻碍神经元发育。鉴于铁过载在认知障碍中的重要性,本研究旨在建立一种铁诱导的斑马鱼认知障碍模型。将斑马鱼暴露于硫酸亚铁(1.5毫克/升、3毫克/升和6毫克/升)中28天。评估了行为参数(Y迷宫、新水箱试验)、氧化应激参数(丙二醛、谷胱甘肽和过氧化氢酶)、乙酰胆碱酯酶(AChE)水平、铁水平和脑匀浆中的白细胞介素-1β(IL-1β)水平。行为和运动反应,特别是在经铁处理28天的斑马鱼中,表明空间记忆丧失和焦虑增加。随着铁浓度的增加,大脑中的活性氧显著增加(p<0.001)。斑马鱼脑匀浆中的脑组织铁含量和IL-1β显著增加(p<0.001)。该模型将有助于筛选治疗性化合物,以加速神经退行性疾病领域的药物发现。

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Development of Zebrafish model for Iron Induced Neuroinflammation.铁诱导神经炎症的斑马鱼模型的建立
Fish Physiol Biochem. 2025 Sep 8;51(5):160. doi: 10.1007/s10695-025-01575-y.

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Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats.镍和铝混合物通过激活氧化应激、环氧化酶-2(COX-2)以及降低雄性白化大鼠大脑皮层和海马体中的乙酰胆碱酯酶(AChE)、脑源性神经营因子(BDNF)和神经生长因子(NGF)水平,引发记忆障碍。
Curr Res Toxicol. 2023 Oct 2;5:100129. doi: 10.1016/j.crtox.2023.100129. eCollection 2023.
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Hydroxyl radical generations form the physiologically relevant Fenton-like reactions.羟自由基的产生形成了具有生理相关性的类 Fenton 反应。
Free Radic Biol Med. 2023 Nov 1;208:510-515. doi: 10.1016/j.freeradbiomed.2023.09.013. Epub 2023 Sep 17.
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Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.剖析神经精神和神经退行性疾病之间的关系。
Mol Neurobiol. 2023 Nov;60(11):6476-6529. doi: 10.1007/s12035-023-03502-9. Epub 2023 Jul 17.
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The Brilliance of the Zebrafish Model: Perception on Behavior and Alzheimer's Disease.斑马鱼模型的卓越之处:对行为与阿尔茨海默病的认知
Front Behav Neurosci. 2022 Jun 13;16:861155. doi: 10.3389/fnbeh.2022.861155. eCollection 2022.
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Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver.衰竭心脏和肝脏中的铁过载、氧化应激与铁死亡
Antioxidants (Basel). 2021 Nov 24;10(12):1864. doi: 10.3390/antiox10121864.
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Antioxidants (Basel). 2021 Jul 30;10(8):1231. doi: 10.3390/antiox10081231.
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Metab Brain Dis. 2021 Oct;36(7):1627-1639. doi: 10.1007/s11011-021-00765-w. Epub 2021 Jul 27.
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The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells.铁螯合剂 PBT434 调节脑微血管内皮细胞的细胞间铁转运。
PLoS One. 2021 Jul 26;16(7):e0254794. doi: 10.1371/journal.pone.0254794. eCollection 2021.
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