Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, College of Pharmacy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
Department of Oncology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453119, China.
Eur J Pharmacol. 2023 Sep 15;955:175874. doi: 10.1016/j.ejphar.2023.175874. Epub 2023 Jun 30.
Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze, Transcranial Doppler TCD, hematoxylin-eosin (HE) staining, Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.
血管性痴呆（VD）是痴呆症最常见的原因之一，占所有病例的约 20%。虽然研究发现硒补充剂可以改善阿尔茨海默病患者的认知能力，但目前尚无关于 VD 引起的认知障碍的研究。本研究旨在探讨无定形硒纳米点（A SeNDs）在预防 VD 中的作用和机制。采用双侧颈总动脉闭塞（BCCAO）方法建立 VD 模型。通过 Morris 水迷宫、经颅多普勒 TCD、苏木精-伊红（HE）染色、神经元特异性核蛋白（Neu N）染色和高尔基染色评估 A SeNDs 的神经保护作用。检测氧化应激和钙调蛋白依赖性蛋白激酶 II（CaMK II）、N-甲基-D-天冬氨酸受体亚基 NR2A、突触后致密蛋白 95（PSD95）的表达水平。最后，测量神经元细胞内钙离子浓度。结果表明，A SeNDs 可显著改善 VD 大鼠的学习记忆能力，恢复大脑后向动脉血流，改善海马 CA1 区锥体神经元的形态和树突重塑，降低 VD 大鼠氧化应激水平，增加 NR2A、PSD95、CaMK II 蛋白的表达，降低细胞内钙离子浓度，但加入选择性 NR2A 拮抗剂 NVP-AAMO77 消除了这些益处。这表明 A SeNDs 可能通过调节 NMDAR 通路改善血管性痴呆大鼠的认知功能障碍。
