Figure 1.

Linagliptin ameliorates cadmium-induced retention and recognition memory impairment in rats. (A) Linagliptin chemical structure. The behavioral study was carried out using the Morris water maze (MWM) paradigm, Y-maze test, and novel object recognition test. (B) During the course of training in the MWM, linagliptin reduced the time needed for animals to reach the submerged platform (escape latency). (C) In the probe test of the MWM, linagliptin improved the retention memory in rats by significantly increasing the time spent in the target quadrant after the removal of the submerged platform. (D) The Y-maze test was used to examine the short-term recognition memory after 1 h of the training session. Herein, linagliptin improved the short-term working memory of rats by increasing the ratio of the time spent in the new/old arm. (E) The novel object recognition test was implemented after 24 h of the training session for the examination of the long-term recognition memory. Herein, linagliptin improved the long-term recognition memory of rats by increasing the discrimination ratio. Relevant to linagliptin’s mode of action, the levels of serum glucose and hippocampal DPP-4 and GLP-1 were studied. Linagliptin elicited no significant effect on serum glucose levels in normoglycemic rats (F) and lowered hippocampal DPP-4 (G) with an elevation in hippocampal GLP-1 (H) in rats. n = 6 in each group (mean ± standard error of the mean). A p-value of less than 0.05 was significant. * p < 0.05, ** p < 0.01, *** p < 0.001, or **** p < 0.0001, compared to control; ^# p < 0.05, ^## p < 0.01, or ^### p < 0.001, compared to cadmium (Tukey’s test for multi-comparisons and one-way ANOVA). Cd, cadmium chloride; DPP-4, dipeptidyl peptidase-4; GLP-1, Glucagon-like peptide-1; LIN, linagliptin.