Regular ArticleIntranasal insulin restores insulin signaling, increases synaptic proteins, and reduces Aβ level and microglia activation in the brains of 3xTg-AD mice

- Intranasal insulin treatment restores brain insulin signaling in 3xTg-AD mice.
- Intranasal insulin increases the levels of synaptic proteins in 3xTg-AD mice.
- Intranasal insulin inhibits microglia activation in the brains of 3xTg-AD mice.
- Intranasal insulin reduces Aβ40 level in the brains of 3xTg-AD mice.
- Our study reveals mechanisms for the efficacy of intranasal insulin treatment.

Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced Aβ40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD.