Artemisinin Ameliorates Diabetic Cognitive Impairment by Improving Synaptic Plasticity via PI3K/Akt Pathway in Mice

Objective The present study was to clarify the improving effect of artemisinin on diabetes-induced cognitive deficit and the underlying mechanisms in mice. Methods Type 2 diabetes mellitus (T2DM) mouse models were established by a single dose of STZ injection (100 mg/kg, i.p.). Those animals were then treated with vehicle or artemisinin (40 mg/kg, i.p.) once daily for 4 weeks. Cognitive performances of the mice were evaluated by novel object recognition, Y maze test and Morris water maze test. After behavioral tests, the expressions of PI3K, Akt, SYN and PSD-95 proteins in the hippocampus were measured by Western blot. Changes in the synaptic ultrastructure of the hippocampalCA1 region were observed by transmission electron microscope. Results Our results indicated that artemisinin significantly ameliorated cognitive deficit in T2DM mice. Furthermore, PI3K and phosphorylated Akt protein levels in the hippocampus of T2DM mice treated with artemisinin were elevated, accompanied with increases in the number of hippocampal neurons, as well as the protein contents of SYN and PSD-95. Meanwhile, synaptic plasticity was also rescued, indicated by an increase in synapse number and synaptic curvature, the thickness of postsynaptic density, and a decrease in the width of synaptic cleft in the hippocampal CA1 region. Conclusion Taken together, these results demonstrate that artemisinin can protect T2DM mice against cognitive decline, at least partially through activating PI3K/Akt pathway to improve synaptic plasticity in the hippocampus. These findings demonstrate that artemisinin may serve as a novel therapeutic agent for diabetic cognitive impairment.