Saral Sinan, Mercantepe Tolga, Topçu Atilla, Kaya Ali Koray, Öztürk Aykut
Department of Physiology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Türkiye.
Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Türkiye.
Life (Basel). 2024 Dec 17;14(12):1672. doi: 10.3390/life14121672.
Dexmedetomidine (DEX) is a selective alpha-2 adrenergic receptor agonist with sedative and anxiolytic properties. Increasing evidence reports that DEX has a neuroprotective effect. In this study, we investigated the potential effects of DEX on learning and memory functions in rats with experimental cognitive impairment. In the study, 21 adult male rats were used. The rats were divided into three groups, namely control, Scopolamine (SCOP) and SCOP + DEX. Cognitive impairment was induced with 1 mg/kg SCOP daily for 21 days. DEX was administered at a dose of 10 µg/kg between days 14 and 21 of the experiment. Following the injections, a spatial memory test was performed with a Morris Water Maze (MWM). At the end of the experiment, the hippocampus was dissected. The brain-derived neurotrophic factor (BDNF), acetylcholine (ACh) and acetylcholinesterase (AChE) levels were determined by ELISA. The tropomyosin receptor kinase B (TrkB) and Cyclic AMP-Response Element-Binding Protein (CREB) levels were measured by immunohistochemistry. DEX treatment improved the learning performance of rats compared to SCOP for 5 days. However, it did not significantly change memory performance. DEX increased the BDNF and ACh levels in the hippocampus while decreasing the AChE levels. Similarly, DEX treatment significantly increased CREB phosphorylation. No significant difference was observed between the TrkB receptor levels of the groups. This study demonstrated that the role of DEX in reducing SCOP-induced cognitive impairment is partially mediated by the increase in BDNF/TrkB/CREB signaling pathway activity.
右美托咪定（DEX）是一种具有镇静和抗焦虑特性的选择性α-2肾上腺素能受体激动剂。越来越多的证据表明，DEX具有神经保护作用。在本研究中，我们调查了DEX对实验性认知障碍大鼠学习和记忆功能的潜在影响。在该研究中，使用了21只成年雄性大鼠。将大鼠分为三组，即对照组、东莨菪碱（SCOP）组和SCOP + DEX组。每天用1 mg/kg SCOP诱导认知障碍，持续21天。在实验的第14天至第21天之间，以10 µg/kg的剂量给予DEX。注射后，用Morris水迷宫（MWM）进行空间记忆测试。实验结束时，解剖海马体。通过ELISA测定脑源性神经营养因子（BDNF）、乙酰胆碱（ACh）和乙酰胆碱酯酶（AChE）水平。通过免疫组织化学测量原肌球蛋白受体激酶B（TrkB）和环磷酸腺苷反应元件结合蛋白（CREB）水平。与SCOP组相比，DEX治疗改善了大鼠5天的学习表现。然而，它并没有显著改变记忆表现。DEX增加了海马体中BDNF和ACh的水平，同时降低了AChE的水平。同样，DEX治疗显著增加了CREB磷酸化。各组之间的TrkB受体水平未观察到显著差异。本研究表明，DEX在减轻SCOP诱导的认知障碍中的作用部分是由BDNF/TrkB/CREB信号通路活性的增加介导的。
