Effects and mechanisms of chloro-oxime derivatives on spatial learning and memory dysfunction in two dementia animal models / 中国药理学通报

ABSTRACT

Aim To explore the effects and mecha-nisms of choro-oxime derivatives on spatial learning and memory impairment in Kunming mice and SD rats induced by scopolamine and Aβ1-42 , respectively. Methods 40 Kunming mice were randomly divided into 5 groups control group, model group, donepezil treatment group, arimoclomol treatment group and TCO-2 treatment group. There were 8 mice in each group. Mice of control group were established by intra-peritoneal injection of saline, and mice of other groups were injected with scopolamine and caused memory im-pairment. Both control group and model group were treated with solvent by intraperitoneal administration;donepezil treatment group received donepezil by intra-gastric administration; arimoclomol treatment group and TCO-2 treatment group were given the correspond-ing drugs by abdominal injection, respectively. The solvent and drugs were given at the same time every morning for 8 days. Spatial learning and memory abili-ty were tested by Morris water maze from the fifth day of the drugs administration. 40 SD rats were divided into 5 groups the same as the dementia model men-tioned above. Mice of control group were established by intracerebroventricular injection of saline, and mice of other groups were injected with insoluble Aβ1-42 to be induced of memory impairment. Solvent and drugs were also delivered as mentioned above. Morris water maze was carried out from the fifth day of the drug de-livery. After that, acetyl cholinesterase activity of hip-pocampus was tested with acetyl cholinesterase reagent kit; the content of Aβ1-42 in hippocampus was meas-ured by ELISA assay kit;the expression of phosphoryl-ated tau proteins was detected by Western Blot. Re-sults In both two dementia models, choro-oxime de-rivatives could improve the spatial learning and memory ability, shorten the escape latency and increase the times of crossing the former platform. Choro-oxime de-rivatives could also inhibit the acetyl cholinesterase ac-tivity in animal brain, decrease the concentration of Aβ1-42 and the expression of phosphorylated tau pro-teins in the dementia rats’ hippocampus. Conclusions Spatial learning and memory deficits induced by sco-polamine and Aβ1-42 could be reversed by choro-oxime derivatives. It may be concerned with enhancement of the cholinergic system functions and reduction of the levels of Aβ1-42 and phosphorylated tau proteins in the brain.