Anti-amnesic effect of ESP-102 on Aβ1–42-induced memory impairment in mice

The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-β (Aβ)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. Aβ1–42 peptide (3 μg/3 μl) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100 mg/kg, p.o), the memory impairment induced by Aβ1–42 peptide was significantly attenuated (P < 0.05). Moreover, ESP-102 (100 mg/kg, p.o) significantly inhibited acetylcholinesterase (AChE) activity in the hippocampus compared to the Aβ1–42 peptide-injected control group. In the subchronic treatment study, ESP-102 (50 or 100 mg/kg/day, p.o) administration for seven days ameliorated the memory impairments induced by Aβ1–42 peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by Aβ1–42 peptide in the hippocampus. Aβ1–42-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 Aβ1–42 peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.

Research Highlights
► Single Aβ injection into the cerebral ventricle causes memory impairment and neural damages.
► Acute ESP-102 administration improves Aβ-induced memory impairment.
► Subchronic ESP-102 administration blocks Aβ-induced inflammation and oxidative damages.