Hojjati Fard Fatemeh, Sabzi Fereshteh, Marefati Narges, Vafaee Farzaneh, Beheshti Farimah, Hashemzadeh Alireza, Darroudi Majid, Hosseini Mahmoud
Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Metab Brain Dis. 2022 Dec;37(8):2719-2733. doi: 10.1007/s11011-022-01073-7. Epub 2022 Sep 9.
Nanoselenium (Nan S) is a form of selenium element that acts with high absorption and low toxicity. However, few studies have examined the effects of Nan S on cognitive impairment. On the other hand, hypothyroidism is a common disease that causes cognitive disorders. Therefore, this study aimed to investigate the effect of Nan S on memory impairment in rats due to propylthiouracil (PTU) - induced hypothyroidism. The roles of brain-derived neurotrophic factor (BDNF), nitric oxide (NO), and oxidative stress were also challenged.
The animals were randomly divided into 4 groups: (1) Control group (normal saline), (2) hypothyroid (Hypo) group: where 0.05% PTU was added to drinking water, (3) and (4) Hypo-Nan S 50, Hypo-Nan S 100 in which 50 or 100 µg/ kg of Nan S were injected respectively. After 6 weeks, spatial and avoidance memory was measured by Morris water maze (MWM) and passive avoidance (PA) tests. The animals then underwent deep anesthesia and the serum samples and the hippocampus and cortex were collected to be used for thyroxin and biochemical measurements including malondialdehyde (MDA), NO, thiol, superoxide dismutase (SOD), catalase (CAT), and BDNF.
The rats showed an increase in the escape latency and traveled path in MWM in the Hypo group compare with the Control group and these parameters were decreased in both Hypo-Nan S 50 and Hypo-Nan S 100 groups compared to the Hypo group. The rats of both Hypo-Nan S 50 and Hypo-Nan S 100 groups spent longer time and traveled longer distances in the target area during the probe trial of MWM than the Hypo group. In addition, the latency to enter the dark box in the PA test was lower in the Hypo group than in the Control group, which was significantly improved after Nan S treatment. Furthermore, the hippocampal and cortical lipid peroxide marker (MDA) levels and NO metabolites of the Hypo group were significantly increased and the antioxidant markers (total thiol, SOD, and CAT) were significantly inhibited compared to the Control group. Compared with the Hypo group, Nan S administration could significantly decrease the oxidant factors and increase the activities antioxidant system and concentration of BDNF.
It is concluded that Nan S might be able to enhance endogenous antioxidant proteins due to its antioxidant activity, thereby improving BDNF and spatial and avoidance memory in the hypothyroidism-induced memory impairment model however, more studies are still necessary to elucidate the exact mechanism(s).
纳米硒（Nan S）是一种硒元素形式，具有高吸收和低毒性的特点。然而，很少有研究考察纳米硒对认知障碍的影响。另一方面，甲状腺功能减退是一种常见的导致认知障碍的疾病。因此，本研究旨在探讨纳米硒对丙硫氧嘧啶（PTU）诱导的甲状腺功能减退大鼠记忆损伤的影响。同时也探讨了脑源性神经营养因子（BDNF）、一氧化氮（NO）和氧化应激的作用。
将动物随机分为4组：（1）对照组（生理盐水）；（2）甲状腺功能减退（Hypo）组：饮用水中添加0.05%的PTU；（3）和（4）Hypo-Nan S 50组、Hypo-Nan S 100组，分别注射50或100μg/kg的纳米硒。6周后，通过莫里斯水迷宫（MWM）和被动回避（PA）试验测量空间和回避记忆。然后对动物进行深度麻醉，收集血清样本以及海马和皮层用于甲状腺素和生化指标的检测，包括丙二醛（MDA）、NO、硫醇、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和BDNF。
与对照组相比，Hypo组大鼠在MWM中的逃避潜伏期和游动路径增加，而与Hypo组相比，Hypo-Nan S 50组和Hypo-Nan S 100组的这些参数均降低。在MWM的探索试验中，Hypo-Nan S 50组和Hypo-Nan S 100组大鼠在目标区域停留的时间更长，游动的距离更远。此外，Hypo组在PA试验中进入暗箱的潜伏期低于对照组，纳米硒治疗后显著改善。此外，与对照组相比，Hypo组海马和皮层脂质过氧化物标志物（MDA）水平和NO代谢产物显著升高，抗氧化标志物（总硫醇、SOD和CAT）显著受到抑制。与Hypo组相比，纳米硒给药可显著降低氧化因子水平，提高抗氧化系统活性和BDNF浓度。
得出结论，纳米硒可能因其抗氧化活性而能够增强内源性抗氧化蛋白，从而改善甲状腺功能减退诱导的记忆损伤模型中的BDNF以及空间和回避记忆，然而，仍需要更多研究来阐明确切机制。
