Dynantia changes of insulin like growth factor-1 signaling pathway in the rat hippocampus following chronic cerebral hypoperfusion

Abstract

Objective To investigate the dynamic changes of hippocampal insulin like growth factor-1 （IGF-1）/IGF-1 receptor （IGF-1R） signaling pathway and learning and memory function and to investigate the possible mechanisms of vascular dementia （VaD）. Methods A rat chronic cerebral hypoperfusion model was induced by using permanent bilateral corranon carotid artery ligation. At day 3, 1 and 2 weeks, 1, 2 and 4 months after modeling, Morris water maze test was used to evaluate the changes of learning and memory function in rats. HE staining was used to observe the morphological changes of hippocampal neurons. Enzyme- linked immunosorbent assay was used to detect the dynamic changes of IGF-1, IGF-1R, Akt and p-Akt in hippocampal tissue. Results One month atter modeling, the rats of a model group began to appear significant learning and memory dysfunction. The numbers of crossing the platform were sigaificant lower than those in a sham operation group （1.91 -± 0. 45 times vs. 3.95 ±1.64 times; t = 17. 251, P = 0. 000）. With the extension of ischemia time, the degree of injury of pyramidal cells in hippocampal CA1 region aggravated gadually in the model group. The levels of IGF-1 and p-Akt in hippocampal tissue increased early after modeling in the model group, and then they declined gradually to the normal levels. The levels of IGF-1 （0. 09 ± 0. 05 ng/mg vs. 0. 20±0. 03 ng/mg; t = - 5. 263, P =0. 003） and p-Akt （12. 50 ± 1.40 pg/mg vs. 17.13 ± 0. 87 pg/mg; t = -5. 651, P =0. 000） at 1 month were sigaificantly lower than those in the sham operation group and continued to 4 months. There were no significant changes in the levels of IGF-1R and Akt. Conclusions The down-regulation of IGF-1/IGF-1R signaling pathway may be one of the pathogeneses of VaD. Key words: Brain Ischerria Dementia, Vascular; Insulin-Like Growth Factor I; Menory Disorders; Rats