Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria; Department of Anatomy, Faculty of Medicine, Trakia University, 11 Armeiska Str, Stara Zagora 6003, Bulgaria; Department of Genes and Behavior, Max Planck Institute of Biophysical Chemistry, Gottingen 37077, Germany.
Horm Behav. 2019 Jan;107:11-19. doi: 10.1016/j.yhbeh.2018.11.007. Epub 2018 Nov 22.
Experimental findings suggest that the melatonin system has a beneficial role in models of Alzheimer's disease (ADs). The aim of the present study was to explore whether the atypical antidepressant agomelatine (Ago), which is a melatonin MT and MT agonist and 5-HT antagonist, is effective against behavioral, biochemical and histological impairments in streptozotocin (STZ)-induced model of ADs in male rats. Male Sprague Dawley rats were treated intraperitoneally (i.p.) with Ago (40 mg/kg) for 30 days starting three months following the intracerebroventricular (icv) injection of STZ. Chronic Ago treatment reduced anxiety-like behavior of STZ-treated rats in the elevated plus maze, increased the preference to saccharine and corrected the spatial memory impairment in the eight-arm radial arm maze test. This melatonin analogue restored STZ-induced biochemical changes, including an increase of beta amyloid (Aβ) protein, and signal markers of inflammation (TNF-alpha and IL-1 beta). Ago exerted partial neuroprotection, specifically in the temporal CA3b subfield of the dorsal hippocampus and temporal piriform cortex. The ability of Ago to alleviate behavioral symptoms and concomitant neuropathological events observed in a model of sporadic ADs suggests that this melatonin alternative can be considered a promising adjuvant in this disease.
实验结果表明，褪黑素系统在阿尔茨海默病（AD）模型中具有有益作用。本研究旨在探讨非典型抗抑郁药阿戈美拉汀（Ago）是否对雄性大鼠脑室内注射链脲佐菌素（STZ）诱导的 AD 模型中的行为、生化和组织学损伤具有治疗作用。雄性 Sprague Dawley 大鼠在侧脑室（icv）注射 STZ 3 个月后，腹腔内（i.p.）给予 Ago（40mg/kg）治疗 30 天。慢性 Ago 治疗可减少 STZ 处理大鼠在高架十字迷宫中的焦虑样行为，增加蔗糖偏好，并纠正在八臂放射臂迷宫测试中的空间记忆障碍。这种褪黑素类似物可恢复 STZ 诱导的生化变化，包括β淀粉样蛋白（Aβ）蛋白和炎症信号标志物（TNF-α和 IL-1β）的增加。Ago 发挥了部分神经保护作用，特别是在背侧海马体的 temporal CA3b 亚区和 temporal 梨状皮层。Ago 减轻散发性 AD 模型中行为症状和伴随神经病理学事件的能力表明，这种褪黑素替代物可被视为该疾病的一种有前途的辅助治疗方法。
