The Role Of Caveolin-1 In Spatial Learning And Memory And Its Mechanism Of Signal Transduction

Caveolins are a family of plasmalemmal vesicles caveolae-associated integral membrane proteins and a marker protein of caveolae involved in the formation and localization that associated with vesicular trafficking,cellular cholesterol homeostasis and signal transduction.There are three caveolin genes expressed in mammals (designated caveolin-1,-2,and -3),and they code for five different isoforms of the protein.Most tissues in the body express at least one of these isoforms.As the principal marker protein of Caveolar domain,Caveolin-1(Cav-1) can construct complexes with other signaling molecules and regulate their activity(e.g.ERα,PKCα) which are involved in endocytosis,cholesterol transport,membrane assembly and signal transduction.In the nervous system,recent studies have confirmed the expression of caveolins in brain and have been linked to the regulation of various neuronal processes, including hippocampal plasticity.Of neuronal vesicular trafficking,Cav-1 can directly interact with VAMP and SNAP25.Caveolin is up-regulated in response to the mechanical and chemical injury of neural cells.In the differentiated PC12 cells and hippocampal neuron Cav-1 highly expresses in the neurite terminal and growth cone. However,the role of Cav-1 in the learning and memory and mechanism remain unclear.Previous works show that after Y-maze training hippocampal Cav-1 up-regulates and consistent with the variance of synaptophysin which indicates Cav-1 is associated with spatial learning and memory,which indicates that Cav-1 may be involved in the learning and memory.The aim of this study was to further investigate the role of caveolin-1 in spatial learning and memory and hippocampal plasticity.We ound out that Cav-1,ERαand other proteins were examined in the hippocampus of young and old SD rats with Western blot after trained for 6 days with Morris water maze.The result showed that Morris water maze training significantly increased Cav-1 protein level in the hippocampus of young and old SD rats(P＜0.05).Also,we investigated the role of Cav-1 in the diabetic mice.The results showed that diabetic induced down-regulation of hippocampal Cav-1 and catalpol can recover its expression.ERα-36 was increased significantly in the both of diabetes group and catalpol-treated group(P＜0.05).In total,as the important signal regulating protein,these results indicate an essential role for caveolins in the membrane-initiated actions of estrogen receptor within the spatial learning and memory and hippocampal plasticity,which may offer valuable evidences and clues to study the role of Cav-1 in the brain.