Qaid Entesar Yaseen Abdo, Abdullah Zuraidah, Zakaria Rahimah, Long Idris
School of Health Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
Histology Department, Faculty of Medicine and Health Sciences, Taiz University, Taiz, Yemen.
Neurochem Res. 2023 May;48(5):1480-1490. doi: 10.1007/s11064-022-03842-3. Epub 2022 Dec 12.
The oxidative stress-induced dysregulation of the cyclic AMP response element-binding protein- brain-derived neurotrophic factor (CREB-BDNF) cascade has been linked to cognitive impairment in several studies. This study aimed to investigate the effect of minocycline on the levels of oxidative stress markers, CREB, and BDNF in lipopolysaccharide (LPS)-induced cognitive impairment. Fifty adult male Sprague Dawley rats were divided randomly into five groups. Group 1 was an untreated control group. Groups 2, 3, 4 and 5 were treated concurrently with LPS (5 mg/kg, i.p) once on day 5 and normal saline (0.7 ml/rat, i.p) or minocycline (25 and 50 mg/kg, i.p) or memantine (10 mg/kg, i.p) once daily from day 1 until day 14, respectively. From day 15 to day 22 of the experiment, Morris Water Maze (MWM) was used to evaluate learning and reference memory in rats. The levels of protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay (ELISA). CREB and BDNF expression and density were measured by immunohistochemistry and western blot analysis, respectively. LPS administration significantly increased escape latency to the hidden platform with decreased travelled distance, swimming speed, target crossings and time spent in the target quadrant. Besides, the hippocampal tissue of LPS rats showed increased levels of PCO and MDA, decreased levels of CAT and SOD, and reduced expression and density of BDNF and CREB. Treatment with minocycline reversed these effects in a dose-dependent manner, comparable to the effects of memantine. Both doses of minocycline treatment protect against LPS-induced cognitive impairment by reducing oxidative stress and upregulating the CREB-BDNF signalling pathway in the rat hippocampus.
多项研究表明，氧化应激诱导的环磷酸腺苷反应元件结合蛋白-脑源性神经营养因子（CREB-BDNF）级联反应失调与认知障碍有关。本研究旨在探讨米诺环素对脂多糖（LPS）诱导的认知障碍中氧化应激标志物、CREB和BDNF水平的影响。将50只成年雄性Sprague Dawley大鼠随机分为五组。第1组为未处理的对照组。第2、3、4和5组分别在第5天腹腔注射一次LPS（5 mg/kg），并从第1天至第14天每天分别腹腔注射一次生理盐水（0.7 ml/只）、米诺环素（25和50 mg/kg）或美金刚（10 mg/kg）。在实验的第15天至第22天，使用莫里斯水迷宫（MWM）评估大鼠的学习和参考记忆。通过酶联免疫吸附测定（ELISA）测定蛋白质羰基（PCO）、丙二醛（MDA）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的水平。分别通过免疫组织化学和蛋白质印迹分析测量CREB和BDNF的表达及密度。给予LPS显著增加了到达隐藏平台的逃避潜伏期，同时行进距离、游泳速度、目标象限穿越次数和在目标象限花费的时间减少。此外，LPS处理的大鼠海马组织中PCO和MDA水平升高，CAT和SOD水平降低，BDNF和CREB的表达及密度降低。米诺环素治疗以剂量依赖的方式逆转了这些作用，与美金刚的作用相当。两种剂量的米诺环素治疗均可通过减轻氧化应激和上调大鼠海马中的CREB-BDNF信号通路来预防LPS诱导的认知障碍。
