School of Medicine, Shahed University, Tehran, Iran.
Department of Anatomy, School of Medicine, Shahed University, Tehran, Iran.
J Chem Neuroanat. 2021 Mar;112:101902. doi: 10.1016/j.jchemneu.2020.101902. Epub 2020 Dec 1.
Uncontrolled diabetes mellitus (DM) is linked to attentional deficits and cognition deterioration. The neurohormone melatonin is an endogenous synchronizer of circadian rhythms with multiple protective properties. This research was designed to assess its effect against learning and memory decline in streptozotocin (STZ)-induced diabetic rats. Rats were assigned to control, melatonin-treated control, diabetic, and melatonin-treated diabetic groups. Melatonin was administered i.p. at a dose of 10 mg/kg/day for 47 days. Treatment of diabetic rats with melatonin reversed decline of spatial recognition memory in Y maze, performance of rats in novel object discrimination, and retention and recall in passive avoidance tasks. Furthermore, melatonin appropriately attenuated hippocampal malondialdehyde (MDA) and reactive oxygen species (ROS) and improved superoxide dismutase (SOD) activity and improved mitochondrial membrane potential (MMP) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with no significant effect on nitrite, glutathione (GSH) and catalase activity. Besides, hippocampal level of acetylcholinesterase (AChE), glial fibrillary acidic protein (GFAP), nuclear factor-kappaB (NF-κB), interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) decreased following melatonin treatment. There was also a reduction of dendritic spines of pyramidal neurons of hippocampal CA1 area in diabetic group that was significantly alleviated upon melatonin treatment. Melatonin could ameliorate learning and memory disturbances in diabetic rats through mitigation of cholinesterase activity, astrocytes, oxidative stress and inflammation and also via upregulation of some antioxidants in addition to its prevention of dendritic spine loss.
未控制的糖尿病（DM）与注意力缺陷和认知能力下降有关。神经激素褪黑素是昼夜节律的内源性同步器，具有多种保护特性。这项研究旨在评估其对链脲佐菌素（STZ）诱导的糖尿病大鼠学习和记忆下降的影响。大鼠被分为对照组、褪黑素治疗对照组、糖尿病组和褪黑素治疗糖尿病组。褪黑素通过腹腔注射给药，剂量为 10mg/kg/天，共 47 天。用褪黑素治疗糖尿病大鼠可逆转 Y 迷宫中空间识别记忆的下降、新物体识别试验中大鼠的表现以及被动回避任务中的保留和回忆。此外，褪黑素适当降低海马丙二醛（MDA）和活性氧（ROS），提高超氧化物歧化酶（SOD）活性，改善线粒体膜电位（MMP）和核因子（红细胞衍生 2）-样 2（Nrf2），对亚硝酸盐、谷胱甘肽（GSH）和过氧化氢酶活性无显著影响。此外，海马乙酰胆碱酯酶（AChE）、胶质纤维酸性蛋白（GFAP）、核因子-kappaB（NF-κB）、白细胞介素 6（IL-6）和肿瘤坏死因子α（TNFα）水平在褪黑素治疗后降低。糖尿病组海马 CA1 区锥体神经元树突棘减少，褪黑素治疗后明显缓解。褪黑素通过减轻胆碱酯酶活性、星形胶质细胞、氧化应激和炎症，以及上调一些抗氧化剂，同时预防树突棘丢失，可改善糖尿病大鼠的学习和记忆障碍。
