Dual co-agonist CI-1206 antagonizes Aβ1-42-induced impairments in spatial learning and memory in mice

Abstract

To study the neuroprotective effects of a novel GIP/GLP-1 receptor dual agonist CI-1206 against Aβ1-42-induced impairments in spatial working memory and long term memory in mice. C57 mice, after receiving intracerebralventricular (i.c.v.) injection of Aβ1-42 and intraperitoneal injection of CI-1206, were divided into the following groups:saline+D-PBS, Aβ1-42+saline, CI-1206+D-PBS and Aβ1-42+CI-1206 group (n=12). Y maze spontaneous alternation of mice was tested to assess short term working memory, and Morris water maze task was used to assess long term reference memory. ①The percentage of right alternation of mice in Aβ1-42+saline group was significantly decreased, while the percentage in Aβ1-42+CI-1206 group was significantly larger than that in Aβ1-42 alone group (P<0.05). ②In Morris water maze test, the escape latency of mice in Aβ1-42+saline group showed a significant increase, with a significant decline in swimming time in target quadrant. Treatment with CI-1206 significantly antagonized these detrimental effects induced by Aβ1-42. ③Aβ1-42 and CI-1206 did not affect the motor ability and vision of mice. I.C.V. administration of Aβ1-42 impaired the short term and long term spatial memory of mice, while CI-1206 could effectively antagonize the detrimental effects.