Protective Effect of Intranasal Insulin Administration on Cognitive Functions and Neurogenesis in a Rat Model of Alzheimer's Disease

Alzheimer's disease is the most common destructive brain disease which is associated with cognitive disorders. Considering the protective role of insulin in the functions of the nervous system, the present study was conducted to investigate the effect of intranasal insulin administration on cognitive disorders and neurogenesis in rats treated with streptozotocin (STZ).

In this experimental study, 32 male Wistar rats were divided into 4 groups of 8: control, STZ, STZ + insulin and insulin. The model of Alzheimer's disease was induced by intraventricular injection of STZ (3 mg/kg; 3 μl in each ventricle). Two weeks after STZ injection, cognitive functions were evaluated using Elevated Plus Maze (EPM) and Passive Avoidance (PA) tests. Insulin treatment (2 IU daily; 10 μl in each nasal passage) was performed after STZ injection for 14 consecutive days. The change in the expression of genes involved in neurogenesis (Nestin, DCX and Ki67) in the hippocampus area was investigated by Real-time PCR technique.

STZ caused longer animal stay in open arms in acquisition phase (64.5±5.24) and recall phase (60.25±5.55) compared to the control group (33±2.17 and 26.38±2.06) in the EPM test (p<0.05 and p<0.01, respectively). In addition, it caused a decrease in learning recall 90 minutes (77.57±6.03) and 24 hours (90.25±7.25) after training, compared to the control group (254.38±3.19 and 238.13±3.46) in the PA test (p<0.001 and p<0.05, respectively). Insulin treatment improved the above parameters in EPM test (41.88±4.14 and 31.5±4.16, respectively) and PA (278.88±2.32 and 218.5±2.12, respectively) compared to the STZ group. STZ also led to a decrease in Nestin gene expression (0.46±0.04), DCX (0.35±0.04) and Ki67 (0.41±0.05) compared to the control group (1.02±0.11, 1±0.04 and 1.01±0.08, respectively) (p<0.01, p<0.001 and p<0.001, respectively), while insulin treatment could increase the expression of these genes (0.87±0.09, 0.78±0.02 and 0.69±0.08, respectively) (p<0.05).

The results showed that insulin improved cognitive functions and increased neurogenesis in rats treated with STZ. Therefore, insulin can be considered as an effective therapeutic target in Alzheimer's disease.