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慢性铝暴露后,通过暴露后自身恢复可逆转氧化应激,改善病理学和神经递质失衡,并挽救大鼠大脑的空间记忆。

Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain.

机构信息

Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Biometals. 2024 Aug;37(4):819-838. doi: 10.1007/s10534-023-00570-1. Epub 2024 Jan 17.

Abstract

Aluminum is a potent neurotoxin, responsible for memory impairment and cognitive dysfunction. The neurotoxic effect of aluminum on cognitive impairment is well documented, however, exposure to aluminum in a time-dependent manner and post-exposure self-recovery still needs to be elaborated. This research aimed to (1) study the time-dependent effect of aluminum exposure by administering a total dose of 5850 mg/kg of Al over two different time periods: 30 and 45 days (130 and 195 mg/kg of AlCl respectively), and (2) study 20 days post-exposure self-recovery effect in both aluminum-exposed groups by giving distilled water. Cognitive abilities were investigated through Morris water maze test and hole board test and compared in both exposure and recovery groups. Oxidative stress markers and neurotransmitter levels were measured for both exposure and recovery groups. To understand the mechanism of aluminum exposure and recovery, immunohistochemical analysis of synaptophysin (Syp) and glial fibrillary acidic protein (GFAP) was performed. Results showed cognitive dysfunction, oxidative stress-induced damage, reduced neurotransmitter levels, decreased immunoreactivity of Syp, and increased GFAP. However, these parameters showed a larger improvement in the recovery group where rats were given aluminum for 30 days period in comparison to recovery group followed by 45 days of aluminum exposure. These results suggest that restoration of cognitive ability is affected by the duration of aluminum exposure. The study findings provide us with insight into the adverse effects of aluminum exposure and can be utilized to guide future preventive and therapeutic strategies against aluminum neurotoxicity.

摘要

铝是一种有效的神经毒素,会导致记忆损伤和认知功能障碍。铝对认知损伤的神经毒性作用已有充分的文献记载,但铝暴露的时间依赖性和暴露后的自我恢复仍需进一步阐述。本研究旨在:(1)通过在两个不同时间段内给予总剂量 5850 mg/kg 的铝来研究铝暴露的时间依赖性效应,即 30 天和 45 天(分别为 130 和 195 mg/kg 的 AlCl);(2)在两个铝暴露组中通过给予蒸馏水研究 20 天暴露后的自我恢复效应。通过 Morris 水迷宫测试和洞板测试研究认知能力,并在暴露组和恢复组之间进行比较。测量暴露组和恢复组的氧化应激标志物和神经递质水平。为了了解铝暴露和恢复的机制,进行了突触素(Syp)和胶质纤维酸性蛋白(GFAP)的免疫组织化学分析。结果显示,认知功能障碍、氧化应激诱导的损伤、神经递质水平降低、Syp 免疫反应性降低和 GFAP 增加。然而,与暴露 45 天相比,暴露 30 天的大鼠在给予铝后恢复组的这些参数显示出更大的改善。这些结果表明,认知能力的恢复受到铝暴露时间的影响。该研究结果为我们提供了关于铝暴露的不良影响的深入了解,并可用于指导针对铝神经毒性的未来预防和治疗策略。

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