Student Research Committee, Kermanshah University of Medical Science, Kermanshah, Iran.
Department of Anatomical Science, Kermanshah University of Medical Science, Kermanshah, Iran.
Eur J Pharmacol. 2023 Aug 15;953:175784. doi: 10.1016/j.ejphar.2023.175784. Epub 2023 May 11.
Alzheimer's disease (AD), as an advanced neurodegenerative disease, is characterized by the everlasting impairment of memory, which is determined by hyperphosphorylation of intracellular Tau protein and accumulation of beta-amyloid (Aβ) in the extracellular space. Minocycline is an antioxidant with neuroprotective effects that can freely cross the blood-brain barrier (BBB). This study investigated the effect of minocycline on the changes in learning and memory functions, activities of blood serum antioxidant enzymes, neuronal loss, and the number of Aβ plaques after AD induced by Aβ in male rats. Healthy adult male Wistar rats (200-220g) were divided randomly into 11 groups (n = 10). The rats received minocycline (50 and 100 mg/kg/day; per os (P.O.)) before, after, and before/after AD induction for 30 days. At the end of the treatment course, behavioral performance was measured by standardized behavioral paradigms. Subsequently, brain samples and blood serum were collected for histological and biochemical analysis. The results indicated that Aβ injection impaired learning and memory performances in the Morris water maze test, reduced exploratory/locomotor activities in the open field test, and enhanced anxiety-like behavior in the elevated plus maze. The behavioral deficits were accompanied by hippocampal oxidative stress (decreased glutathione (GSH) peroxidase enzyme activity and increased malondialdehyde (MDA) levels in the brain (hippocampus) tissue), increased number of Aβ plaques, and neuronal loss in the hippocampus evidenced by Thioflavin S and H&E staining, respectively. Minocycline improved anxiety-like behavior, recovered Aβ-induced learning and memory deficits, increased GSH and decreased MDA levels, and prevented neuronal loss and the accumulation of Aβ plaques. Our results demonstrated that minocycline has neuroprotective effects and can reduce memory dysfunction, which are due to its antioxidant and anti-apoptotic effects.
阿尔茨海默病（AD）是一种高级神经退行性疾病，其特征是记忆持久受损，这是由细胞内 Tau 蛋白的过度磷酸化和细胞外空间中β-淀粉样蛋白（Aβ）的积累决定的。米诺环素是一种具有神经保护作用的抗氧化剂，可自由穿过血脑屏障（BBB）。本研究探讨了米诺环素对 Aβ 诱导 AD 后雄性大鼠学习记忆功能变化、血清抗氧化酶活性、神经元丢失和 Aβ 斑块数量的影响。健康成年雄性 Wistar 大鼠（200-220g）随机分为 11 组（n=10）。大鼠在 AD 诱导前、后和前/后给予米诺环素（50 和 100mg/kg/天；口服（P.O.））30 天。治疗疗程结束后，通过标准化行为范式测量行为表现。随后收集脑样本和血清进行组织学和生化分析。结果表明，Aβ 注射损害了 Morris 水迷宫测试中的学习和记忆表现，降低了旷场测试中的探索/运动活动，并增强了高架十字迷宫中的焦虑样行为。行为缺陷伴随着海马氧化应激（脑（海马）组织中谷胱甘肽过氧化物酶酶活性降低和丙二醛（MDA）水平升高）、Aβ 斑块数量增加和海马神经元丢失，分别由 Thioflavin S 和 H&E 染色证实。米诺环素改善了焦虑样行为，恢复了 Aβ 引起的学习和记忆缺陷，增加了 GSH 并降低了 MDA 水平，并防止了神经元丢失和 Aβ 斑块的积累。我们的结果表明，米诺环素具有神经保护作用，可减少记忆功能障碍，这归因于其抗氧化和抗细胞凋亡作用。
