褪黑素是松果体分泌的激素,它可能与昼夜节律有关,衰老和神经保护。褪黑激素水平在散发性阿尔茨海默病(sAD)患者中降低,这表明了褪黑能系统和sAD之间的关系。褪黑素可以减少炎症,氧化应激,TAU蛋白过度磷酸化,和β-淀粉样蛋白(Aβ)聚集体的形成。因此,这项工作的目的是研究用10mg/kg褪黑激素治疗的影响(i。p)在脑室内(ICV)输注3mg/kg链脲佐菌素(STZ)诱导的sAD动物模型中。ICV-STZ引起大鼠大脑的变化,类似于sAD患者的变化。这些变化包括;进行性记忆下降,神经原纤维缠结的形成,老年斑,葡萄糖代谢紊乱,胰岛素抵抗,甚至反应性星形胶质细胞增生,其特征是葡萄糖水平和胶质纤维酸性蛋白(GFAP)的上调。结果表明,在STZ输注30天后,ICV-STZ在大鼠中引起短期空间记忆障碍,而没有运动能力障碍,这在损伤后第27天进行了评估。此外,我们观察到,在Y-迷宫测试中,用褪黑激素延长30天的治疗可以改善动物的认知障碍,但不在对象位置测试中。最后,我们证明,接受ICV-STZ的动物在海马中具有高水平的Aβ和GFAP,用褪黑激素治疗可降低Aβ水平,但不降低GFAP水平。结论褪黑激素可能有助于控制大脑中淀粉样蛋白病理的进展。
Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer\'s disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of β-amyloid (Aβ) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10 mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3 mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aβ and GFAP in the hippocampus and that treatment with melatonin reduces Aβ levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.