Melatonin attenuates streptozotocin-induced Alzheimer-like features in hyperglycemic rats. (January 2020)

• Record Type: Journal Article
• Authors: Kamsrijai, Utcharaporn; Wongchitrat, Prapimpun; Nopparat, Chutikorn; Satayavivad, Jutamaad; Govitrapong, Piyarat
• Is Part Of: Neurochemistry international. Volume 132(2020)
• Publication Date: 2020-01
• Subjects: Alzheimer's -- Diabetes -- Hippocampus -- Insulin receptors -- Melatonin; AD Alzheimer's disease -- ADAM10 a disintegrin and metalloproteinase domain-containing protein 10 -- APP amyloid precursor protein -- Aβ amyloid β -- Aβ42 amyloid beta 42 peptide -- BACE1 β-site APP-cleaving enzyme 1 -- C99 β-cleaved C-terminal fragment -- DM Diabetes mellitus -- GSK-3β glycogen synthase kinase-3β -- HFD high-fat diet -- IRS1 insulin receptor substrate 1 -- IRβ insulin receptor β -- Mel Melatonin -- MT1 melatonin receptor 1 -- MT2 melatonin receptor 2 -- MWM Morris water maze -- PS1 presinilin1 -- STZ streptozotocin; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.104601
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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. Highlights: Melatonin ameliorates memory deficits in STZ-induced hyperglycemia rats. Melatonin decreased formation of Aβ42 peptide in STZ-induced hyperglycemia rats. Melatonin decreased formation of p-tau in STZ-induced hyperglycemia rats. Melatonin prevented the induction of BACE1 and PS1 induced by hyperglycemia. Melatonin prevented the reduction of ADAM10 induced by hyperglycemia.