Anti-amnesic effect of ESP-102 on A beta(1-42)-induced memory impairment in mice

作者：Kim Dong Hyun; Jung Won Young; Park Se Jin; Kim Jong Min; Lee Seungjoo; Kim Young Choong; Ryu Jong Hoon^*

来源：Pharmacology Biochemistry and Behavior, 2010, 97(2): 239-248.

DOI：10.1016/j.pbb.2010.08.005

• ESP-102
• Amyloid-beta protein
• Acetylcholinesterase
• Learning and memory
• Neuroprotection

The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-beta (A beta)(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. A beta(1-42) peptide (3 mu g/3 mu l) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100 mg/kg, p.o), the memory impairment induced by A beta(1-42) 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 A beta(1-42) 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 A beta(1-42) peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by A beta(1-42) Peptide in the hippocampus. A beta(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 A beta(1-42) peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.

• 出版日期2010-12