Changes Of The Learning And Memory Function And IGF-â…  Signal Pathway In Hippocampus Of Diabetic Rats

Objective Diabetic encephalopathy is one of the diabetic chronic complications, characterized by learning and memory dysfunction. In central neuron system, hippocampus is associated with the ability of learing and memory, so the pathogenesis of diabetic encephalopathy may be result from structure and function degeneration in hippocampus. This study was performed to investigate the changes of learning and memory function and IGF-Ⅰ, Akt and caspase3 in hippocampus of diabetic rats.Methods Twelve male Sprague-Dawley (SD) rats weighing 200-250g were randomly divided into two groups: controls (NC, n=6) and diabetes (DM, n=6). The diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ). Fasting blood glucose monitored by tail-vein sampling≥16.7mmol/L was our criterion for experimental diabetes. Before and 12 weeks after the models were established, the ability of learning and memory function were measured by the Morris water maze testing. The next day after twelve-week rats'Morris water maze testing, fasting blood was taken from heart and used to be examed blood glucose and glycosylated hemoglobin (HbA1c). Then both hippocampus were harvested, the left one was measured at tissue mRNA level and the right one was treated with prarffin-embeded tissue slides and for immunohistochemical assay. The expressions of IGF-Ⅰand p-Akt were evaluated by relative quantity RT-PCR and immunohistochemistry in rats'hippocampus CA1 region.Results1. The hyperglycemia, HbA1c-increasing, bodyweight-losing ofdiabetic rats were significantly difference with those of NC group (P<0.01).2. At the start of the study, both the average of escape latency time and swimming distance in the DM group (20.3±13.7s, 429.6±297.4cm) were similar to NC group (20.8±14.9s, 404.9±286.9cm, P>0.05). 12 weeks later, the average of escape latency time in the DM group (8.4±5.1s) were similar to NC group (6.5±4.0s, P>0.05), while the average of swimming distance in the DM group (214.0±129.2cm) were much longer than NC group (144.0±94.0cm, P<0.05).3. 12 weeks after diabetes, the IGF-ⅠmRNA contents in hippocampus CA1 region of rats in the DM group (0.24±0.03) were reduced compared with that in the DM group (0.31±0.08, P<0.05); the Akt1 mRNA contents in the DM group (0.99±0.27) were much less than that in the NC group (1.67±0.27, P<0.01).4. Immunohistochemical results showed that in the hippocampus CA1 region, IGF-Ⅰexpression-positive neurons in the DM group (0.172±0.007) were much less than that in the NC group (0.202±0.019, P<0.01); there were no significant differences of p-Akt positive neurons between the DM group (0.197±0.021) and the NC group (0.176±0.032, P>0.05); caspase3 positive neurons in the DM group (0.120±0.016) were much more than that in the NC group (0.100±0.012, P<0.05).Conclusions1. The abilities of learning and memory of 12-week diabetic rats are slightly degraded.2. In the hippocampus of 12-week diabetic rats, the down regulation of IGF-Ⅰwith changes of its signal pathway inducing the apoptosis of neurons may participate in the pathogenesis of diabetic encephalopathy.