The effect of Glycogen synthase kinase-3 inhibition on dysfunction of the learning and memory and anxiety emotion after rat’s chronic cerebral ischemia

Abstract

Objective To explore the roles of glycogen synthase kinase-3β(GSK-3β) in cognitive dysfunction and emotional alterations after rat’s chronic cerebral ischemia. Methods 51 SD rats were randomly divided into sham group (sham group, n=17), chronic cerebral ischemia group (2VO group, n=17), chronic cerebral ischemia group + LiCl group (2VO + LiCl group, n=17), according to the table of random number. All groups were intraperitoneally injected with LiCl or saline on 3rd, 7th, 14th, 21st and 28th day, and then produced the chronic cerebral ischemia models. On the 28th day after model, the spatial learning and memory, fear memory, and anxiety emotion were detected. Results The Morris water maze test showed that 2VO group spent longer latent time searching and finding the platform than sham group (4th day P<0.01, 3rd, 5th, 6th, 7th day P<0.05). 2VO+ LiCl group spent shorter latent time than 2VO group (4th day P<0.01, 5th, 6th, 7th day P<0.05). After removing the platform, 2VO group spent longer time arriving the former location than sham group (P<0.05). And 2VO+ LiCl group spent dramatically different time compared to 2VO group (P<0.01). Step-down test showed 2VO group spent shorter latent time than sham group (2VO group: (41.00±1.87)s, sham group: (44.55±2.77)s)(P<0.05). 2VO+ LiCl group spent dramatically longer latent time compared to 2VO group(2VO+ LiCl group: (43.40±1.35)s)(P<0.05). 2VO group made much more mistakes times than sham group (P<0.05). 2VO+ LiCl group made dramatically less mistakes times compared to 2VO group (P<0.05). The elevated plus maze test showed 2VO group had much less ratio of retention time in open arms (among total arms retention time) than sham group(2VO group: (0.23±0.01), sham group: (0.25±0.01))(P<0.01). 2VO+ LiCl group had much larger ratio than 2VO group(2VO+ LiCl group: (0.24±0.01), P<0.05). 2VO group had much less ratio of entry times in open arms (among total arms entry times) than sham group (P<0.01). 2VO+ LiCl group had much larger ratio than 2VO group(P<0.05). Conclusion Chronic cerebral ischemia can lead to deterioration of learning and memory, and anxiety emotion for rats. However, inhibition of GSK-3β can ameliorate these alterations. Key words: Chronic cerebral ischemia; GSK-3β; Dysfunction of learning and memory; Anxiety