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α-硫辛酸可逆转东莨菪碱诱导的Wistar大鼠前额叶皮质空间记忆丧失和锥体细胞神经变性。

Alpha lipoic acid reverses scopolamine-induced spatial memory loss and pyramidal cell neurodegeneration in the prefrontal cortex of Wistar rats.

作者信息

Memudu Adejoke Elizabeth, Adanike Rukky Precious

机构信息

Department of Anatomy, Faculty of Basic Medical Science, Edo State University, Uzairue, Nigeria.

Department of Anatomy, Faculty of Basic Medical Sciences, Bingham University, P.M.B 005, Karu, Nasarawa State, Nigeria.

出版信息

IBRO Neurosci Rep. 2022 May 20;13:1-8. doi: 10.1016/j.ibneur.2022.05.005. eCollection 2022 Dec.

Abstract

Neurodegenerative disorders are linked to oxidative tissue damage characterized by gradual loss of cognitive functions and neuronal cells. Alpha-lipoic acid (AHA) has a strong antioxidant property. Scopolamine is an anti-muscarinic agent used to study the mechanism of memory loss in an animal model. This study is aimed at evaluating the antioxidant role of alpha lipoic acid in reversing scopolamine induced memory loss and neurodegenerative process in the prefrontal cortex of Wistar rats. Twenty adult male Wistar rats used were divided into four groups (n = 5): Group 1 received vehicle (Control), Group 2 had scopolamine (1 mg/kg, i.p) for 4 days, Group 3 received AHA (200 mg/kg, p.o) for 10 days while Group 4 were pretreated with scopolamine (1 mg/kg, i.p) for 4 days followed by oral administration of 200 mg/kg of AHA for 10 days. The rats were subjected to Y-maze test to assess their spatial memory. The rats were euthanized, the prefrontal area was excised and fixed in 10% formol-calcium and processed for Haematoxylin and Eosin, Cresyl fast violet for Nissl Bodies (Ribosome), and Glial Fibrillary Acidic Protein (GFAP) stains. Scopolamine caused a significant decline in spatial working memory, prefrontal neuron cell loss, and increased proliferation of reactive astrocytes (astrogliosis) when compared with the control and AHA treated group. AHA process of reversing scopolamine-induced memory deficit, prefrontal neuron cell loss, and generation of reactive astrocytes (astrogliosis) is mediated by its antioxidant mediated positive modulation of astrocyte-neuronal interaction during neuroinflammation in response to oxidative tissue damage.

摘要

神经退行性疾病与以认知功能和神经元细胞逐渐丧失为特征的氧化组织损伤有关。α-硫辛酸(AHA)具有很强的抗氧化特性。东莨菪碱是一种抗毒蕈碱剂,用于在动物模型中研究记忆丧失的机制。本研究旨在评估α-硫辛酸在逆转东莨菪碱诱导的Wistar大鼠前额叶皮质记忆丧失和神经退行性过程中的抗氧化作用。所使用的20只成年雄性Wistar大鼠被分为四组(n = 5):第1组接受赋形剂(对照组),第2组连续4天腹腔注射东莨菪碱(1 mg/kg),第3组连续10天口服AHA(200 mg/kg),而第4组先连续4天腹腔注射东莨菪碱(1 mg/kg),随后连续10天口服2百mg/kg的AHA。对大鼠进行Y迷宫测试以评估其空间记忆。将大鼠安乐死,切除前额叶区域并固定在10%的甲醛钙中,然后进行苏木精和伊红染色、用于尼氏体(核糖体)的甲酚紫快速染色以及胶质纤维酸性蛋白(GFAP)染色。与对照组和AHA治疗组相比,东莨菪碱导致空间工作记忆显著下降、前额叶神经元细胞丢失以及反应性星形胶质细胞增殖增加(星形胶质细胞增生)。AHA逆转东莨菪碱诱导的记忆缺陷、前额叶神经元细胞丢失以及反应性星形胶质细胞(星形胶质细胞增生)生成的过程是通过其抗氧化介导的在神经炎症期间对星形胶质细胞-神经元相互作用的正向调节来实现的,这种神经炎症是对氧化组织损伤的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9285/9157193/d35c68d31e23/gr4.jpg

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