Zhou Xiao-Yan, Zhang Fang, Hu Xiao-Tong, Chen Jing, Tang Ren-Xian, Zheng Kui-Yang, Song Yuan-Jian
Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
Brain Res. 2017 Feb 15;1657:262-268. doi: 10.1016/j.brainres.2016.12.018. Epub 2016 Dec 22.
The critical factor considered in a depression induced by diabetes is the inflammation eliciting hippocampal, amygdala and thalamic neuronal injury. Therefore, inhibiting inflammatory reactions in the brain and reducing neuronal injury can alleviate depression in rodents suffering from diabetes mellitus. The oral administration of astaxanthin has been employed in emotional disorders and diabetic complications due to its anti-depressant, anti-inflammatory and anti-apoptotic functions. However, it has not been reported whether astaxanthin can improve diabetes-related depression-like behavior, and its potential mechanisms have not been elucidated. The objective of the present study is to elucidate the effect of astaxanthin on depression in diabetic mice and to understand the underlying molecular mechanisms. In this study, experimental diabetic mice were given a single intraperitoneal injection of streptozotocin (STZ, 150mg/kg, dissolved in citrate buffer) after fasting for 12h. The diabetic model was assessed 72h after STZ injection, and mice with a fasting blood glucose level more than or equal to 16.7mmol/L were used in this study, and oral astaxanthin (25mg/kg) was provided uninterrupted for ten weeks. Depression-like behavior was evaluated by the tail suspension test (TST) and forced swimming test (FST). The glial fibrillary acidic protein (GFAP) and cleaved caspase-3-positive cells were measured by immunohistochemistry, and the western blotting was used to test the protein levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase (COX-2). The results showed that astaxanthin had an anti-depressant effect on diabetic mice. Furthermore, we observed that astaxanthin significantly reduced the number of GFAP-positive cells in the hippocampus and hypothalamus, and also the expression of cleaved caspase-3 in the hippocampus, amygdala and hypothalamus was decreased as well. Moreover, astaxanthin could down-regulate the expression of IL-6, IL-1β and COX-2 in the hippocampus. These findings suggest that the mechanism of astaxanthin in preventing depression in diabetic mice involves the inhibition of inflammation/inflammation inhibition, thereby protecting neurons in hippocampus, amygdala and hypothalamus against hyperglycemic damage.
糖尿病诱发抑郁症时考虑的关键因素是引发海马体、杏仁核和丘脑神经元损伤的炎症。因此，抑制大脑中的炎症反应并减少神经元损伤可以缓解糖尿病啮齿动物的抑郁症。虾青素因其抗抑郁、抗炎和抗凋亡功能，已被用于治疗情绪障碍和糖尿病并发症。然而，尚未有关于虾青素是否能改善糖尿病相关抑郁样行为的报道，其潜在机制也尚未阐明。本研究的目的是阐明虾青素对糖尿病小鼠抑郁症的影响，并了解其潜在的分子机制。在本研究中，实验性糖尿病小鼠在禁食12小时后腹腔注射一次链脲佐菌素（STZ，150mg/kg，溶解于柠檬酸盐缓冲液中）。在注射STZ后72小时评估糖尿病模型，本研究使用空腹血糖水平大于或等于16.7mmol/L的小鼠，并连续十周口服虾青素（25mg/kg）。通过悬尾试验（TST）和强迫游泳试验（FST）评估抑郁样行为。通过免疫组织化学测量胶质纤维酸性蛋白（GFAP）和裂解的半胱天冬酶-3阳性细胞，并使用蛋白质印迹法检测白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和环氧化酶（COX-2）的蛋白质水平。结果表明，虾青素对糖尿病小鼠具有抗抑郁作用。此外，我们观察到虾青素显著减少了海马体和下丘脑GFAP阳性细胞的数量，海马体、杏仁核和下丘脑裂解的半胱天冬酶-3的表达也降低了。此外，虾青素可以下调海马体中IL-6、IL-1β和COX-2的表达。这些发现表明，虾青素预防糖尿病小鼠抑郁症的机制涉及抑制炎症/炎症抑制，从而保护海马体、杏仁核和下丘脑的神经元免受高血糖损伤。
