The Effect of Imipramine on Memory Disorder in a Rat Model of Alzheimer’s Disease: Involvement of Insulin Signaling Pathway and Reelin Protein

Alzheimer's disease (AD) is a progressive neurological disorder that impairs cognitive functions. Imipramine is an antidepressant drug with antioxidant and anti-inflammatory effects on the brain. The present study aimed to investigate the effect of imipramine on memory impairment, focusing on insulin signaling pathway and synaptic plasticity in rats treated with streptozotocin (STZ).

In this experimental study, 32 male Wistar rats were divided into 4 groups: control, STZ, STZ+imipramine, and imipramine. An animal model of AD was induced by intraventricular injection of STZ (3mg/kg; 3μl/ventricle). Elevated plus maze and passive avoidance tests were used to examine cognitive functions. 24 h after STZ injection, treatment with imipramine (20mg/kg) was done intraperitoneally for 14 days. The expression level of insulin and the factors involved in the insulin signaling pathway (IR, IRS2, PI3K, Akt, and mTOR) were investigated by Real-time PCR and the protein level of Reelin (a factor involved in synaptic plasticity) was evaluated by western blot technique. One-way analysis of variance and Tukey's post hoc test were used to analyze the data.

The results showed that STZ caused memory disorders in rats and decreased the expression level of insulin and factors involved in the insulin signaling pathway, and also the protein level of Reelin. In contrast, imipramine reduced memory disorders and increased the expression of the mentioned factors in the hippocampus of animals treated with STZ.

Imipramine appears to reduce memory disorders in STZ-treated animals through its effects on the insulin signaling pathway and protein involved in synaptic plasticity.