Nabavi Zadeh Fatemeh, Nazari Maryam, Amini Abdollah, Adeli Soheila, Barzegar Behrooz Amir, Fahanik Babaei Javad
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Front Neurosci. 2023 Apr 20;17:1073369. doi: 10.3389/fnins.2023.1073369. eCollection 2023.
Most dementia cases in the elderly are caused by Alzheimer's disease (AD), a complex, progressive neurological disease. Intracerebroventricular (ICV) administration of streptozotocin (STZ) in rat's results in aberrant brain insulin signaling, oxidative stress, and mitochondrial dysfunction that impair cognition change neural plasticity, and eventually lead to neuronal death. The current study aims to define the neuroprotective action of alpha-tocopherol in enhancing mitochondrial function and the function of synapses in memory-impaired rats brought on by icv-STZ.
Male Wistar rats were pre-treated with (α-Tocopherol 150 mg/kg) orally once daily for 7 days before and 14 days after being bilaterally injected with icv-STZ (3 mg/kg), while sham group rats received the same volume of STZ solvent. After 2 weeks of icv-STZ infusion, rats were tested for cognitive performance using a behaviors test and then were prepared electrophysiology recordings or sacrificed for biochemical and histopathological assays.
The cognitive impairment was significantly minimized in the behavioral paradigms for those who had taken α-Tocopherol. In the hippocampus of icv-STZ rat brains, α-Tocopherol ocopherol effectively prevented the loss of glutathione levels and superoxide dismutase enzyme activity, lowered mitochondrial ROS and mitochondrial membrane potential, and also brought about a decrease in Aβ aggregation and neuronal death.
Our findings demonstrated that by lowering neurobehavioral impairments caused by icv-STZ, oxidative stress, and mitochondrial dysfunction, α-Tocopherol enhanced intracellular calcium homeostasis and corrected neurodegenerative defects in the brain. These findings examine the available approach for delaying AD connected to mitochondrial malfunction and plasticity issues.
大多数老年痴呆病例是由阿尔茨海默病（AD）引起的，这是一种复杂的、进行性的神经疾病。给大鼠脑室内注射链脲佐菌素（STZ）会导致异常的脑胰岛素信号传导、氧化应激和线粒体功能障碍，这些会损害认知、改变神经可塑性，并最终导致神经元死亡。本研究旨在确定α-生育酚在增强由脑室内注射STZ导致记忆受损大鼠的线粒体功能和突触功能方面的神经保护作用。
雄性Wistar大鼠在双侧注射脑室内STZ（3mg/kg）前7天及注射后14天，每天口服一次α-生育酚（150mg/kg），而假手术组大鼠接受相同体积的STZ溶剂。在脑室内注射STZ两周后，使用行为测试对大鼠的认知能力进行测试，然后进行电生理记录或处死以进行生化和组织病理学分析。
服用α-生育酚的大鼠在行为范式中的认知障碍明显减轻。在脑室内注射STZ的大鼠脑海马中，α-生育酚有效地防止了谷胱甘肽水平和超氧化物歧化酶活性的丧失，降低了线粒体活性氧和线粒体膜电位，还减少了β-淀粉样蛋白（Aβ）聚集和神经元死亡。
我们的研究结果表明，α-生育酚通过降低脑室内注射STZ、氧化应激和线粒体功能障碍引起的神经行为损伤，增强了细胞内钙稳态并纠正了大脑中的神经退行性缺陷。这些研究结果探讨了延缓与线粒体功能障碍和可塑性问题相关的AD的现有方法。
