Kim_2010_Pharmacol.Biochem.Behav_97_239

The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-beta (Abeta)(1-42) peptide in mice. The ameliorating effect of ESP-102 on memory impairment was investigated using the passive avoidance and the Morris water maze tasks, and the pathological changes were identified by immunohistochemistry and western blotting. Abeta(1-42) peptide (3mug/3mul) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100mg/kg, p.o), the memory impairment induced by Abeta(1-42) peptide was significantly attenuated (P<0.05). Moreover, ESP-102 (100mg/kg, p.o) significantly inhibited acetylcholinesterase (AChE) activity in the hippocampus compared to the Abeta(1-42) peptide-injected control group. In the subchronic treatment study, ESP-102 (50 or 100mg/kg/day, p.o) administration for seven days ameliorated the memory impairments induced by Abeta(1-42) peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by Abeta(1-42) peptide in the hippocampus. Abeta(1-42)-induced increases in the expression of GFAP (an astrocyte marker) and inducible nitric oxide synthase (iNOS) in the hippocampal region were also attenuated by ESP-102 treatment. These results suggest that the ameliorating effect of ESP-102 on Abeta(1-42) peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.