Diabetes mellitus (DM) is increasingly recognized as a risk for developing of Alzheimer's disease (AD). Accordingly, it has been reported that melatonin level is disturbed in both DM and AD which indicates its involvement in the pathophysiology of these diseases. In this study, the neuroprotective activities and relevant mechanisms of melatonin were evaluated in diabetic rat model. Rats were subcutaneously injected with melatonin (10 mg/kg) for 42 consecutive days. Single dose of streptozotocin (60 mg/kg STZ) was intraperitoneally injected. Morris water maze, Western blot and immunohistochemistry analysis of proteins in the hippocampus were measured. We found that melatonin was effective in protecting against memory impairment and decreased formation of Aβ42 peptide and phosphorylated tau in the hippocampus of STZ-treated rats. Melatonin significantly restored the reduction in phospho-insulin receptor β (p-IRβ) and ameliorated the increase of inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) in STZ-treated rats. Furthermore, it restored the phosphorylation of glycogen synthase kinase 3β (GSK3β), indicating a decreased activity of GSK3β. Melatonin prevented amyloidogenic processing of β-amyloid precursor protein (βAPP) by significantly inhibited β-site APP cleaving enzyme (BACE1), presenilin 1 (PS1), and β-cleaved C-terminal fragment (C99). In conclusion, melatonin ameliorates memory deficits in STZ-induced hyperglycemia rats by restoring insulin signaling pathway which is independent of its effects on blood glucose and insulin levels. Thus, melatonin might be a therapeutic option for helping patients suffering from diabetes and contributed to Alzheimer's disease.

中文翻译：

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褪黑素减弱了高血糖大鼠中链脲佐菌素诱导的阿尔茨海默氏样特征。

糖尿病（DM）日益被认为是患阿尔茨海默氏病（AD）的风险。因此，据报道，DM和AD中的褪黑激素水平受到干扰，这表明其参与了这些疾病的病理生理。在这项研究中，评估了褪黑激素在糖尿病大鼠模型中的神经保护活性及其相关机制。给大鼠连续42天皮下注射褪黑激素（10 mg / kg）。腹膜内注射单剂量的链脲佐菌素（60 mg / kg STZ）。测量了莫里斯水迷宫，蛋白质印迹和海马蛋白质的免疫组织化学分析。我们发现褪黑激素可有效预防STZ治疗的大鼠海马的记忆障碍和减少Aβ42肽和磷酸化tau的形成。褪黑素可显着恢复磷酸胰岛素受体β（p-IRβ）的减少，并改善STZ治疗的大鼠中胰岛素受体底物1（IRS1）抑制性磷酸化的增加。此外，它恢复了糖原合酶激酶3β（GSK3β）的磷酸化，表明GSK3β的活性降低。褪黑素通过显着抑制β位APP裂解酶（BACE1），早老素1（PS1）和β裂解的C端片段（C99）来阻止β淀粉样前体蛋白（βAPP）的淀粉样生成过程。总之，褪黑激素通过恢复胰岛素信号通路来改善STZ诱导的高血糖大鼠的记忆障碍，而胰岛素信号通路与其对血糖和胰岛素水平的影响无关。因此，