Tamam Yusuf, Yokuş Beran, Tamam Cüneyt, Yüceer Hande, Karahan Selim, Em Bernan, Tamam Şerife Banu, Tüzün Erdem
Dicle University, Faculy of Medicine, Department of Neurology, Diyarbakır, Turkey.
Dicle University, Faculy of Veterinary Medicine, Department of Biochemistry, Diyarbakır, Turkey.
Noro Psikiyatr Ars. 2023 Feb 18;60(1):68-72. doi: 10.29399/npa.28112. eCollection 2023.
Alzheimer's disease (AD) is a neurodegenerative disease caused by the accumulation of amyloid plaques in the cerebral cortex and hippocampus. In this study, the effects of local anesthetic lidocaine on neurodegeneration markers and memory were investigated for the first time in streptozotocin-induced rat AD model.
Streptozotocin (STZ) was administered intracerebroventricularly (ICV) into Wistar rats to develop AD model. For lidocaine group (n=14), lidocaine (5 mg/kg) was administered intraperitoneally (IP) in addition to STZ injection. Control group animals (n=9) were treated with saline for 21 days. Morris Water Maze (MWM) test was performed to evaluate memory after the injections were completed. Also, the serum levels of TAR DNA-binding protein-43 (TDP-43), amyloid precursor protein (APP), β-secretase 1, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), response element binding protein (CREB), c-FOS were measured using ELISA test and compared between groups.
Lidocaine group animals showed lower escape latency and time in quadrant scores in MWM inferring better memory performance. Furthermore, lidocaine administration caused a significant decline in TDP-43 levels. However, the expression of APP and β-secretase were significantly higher in AD and lidocaine groups compared to control group. Moreover, lidocaine group markedly had higher serum NGF, BDNF, CREB, and c-FOS levels compared to those in the AD group.
In addition to neuroprotective effects in STZ-induced AD model, Lidocaine also appears to improve memory. This effect might be associated with increased levels of several growth factors and associated intracellular molecules. The therapeutic role of lidocaine in the pathophysiology of AD should be studied in the future.
阿尔茨海默病（AD）是一种由淀粉样斑块在大脑皮层和海马体中积累引起的神经退行性疾病。在本研究中，首次在链脲佐菌素诱导的大鼠AD模型中研究了局部麻醉药利多卡因对神经退行性变标志物和记忆的影响。
将链脲佐菌素（STZ）脑室内注射（ICV）到Wistar大鼠体内以建立AD模型。利多卡因组（n = 14）除注射STZ外，还腹腔注射（IP）利多卡因（5 mg/kg）。对照组动物（n = 9）用生理盐水治疗21天。注射完成后进行莫里斯水迷宫（MWM）试验以评估记忆。此外，使用酶联免疫吸附测定（ELISA）试验测量血清中TAR DNA结合蛋白43（TDP-43）、淀粉样前体蛋白（APP）、β-分泌酶1、神经生长因子（NGF）、脑源性神经营养因子（BDNF）、反应元件结合蛋白（CREB）、c-FOS的水平，并在组间进行比较。
利多卡因组动物在MWM试验中的逃避潜伏期和象限得分时间较低，表明记忆表现更好。此外，利多卡因给药导致TDP-43水平显著下降。然而，与对照组相比，AD组和利多卡因组中APP和β-分泌酶的表达显著更高。此外，与AD组相比，利多卡因组血清NGF、BDNF、CREB和c-FOS水平明显更高。
除了在STZ诱导的AD模型中具有神经保护作用外，利多卡因似乎还能改善记忆。这种作用可能与几种生长因子和相关细胞内分子水平的增加有关。利多卡因在AD病理生理学中的治疗作用有待未来研究。
