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.