Ameliorative effects of a neuroprotective agent, T-817MA, on place learning deficits induced by continuous infusion of amyloid-β peptide (1–40) in rats
✍ Scribed by Phuong Thi Hong Nguyen; Tatsuo Kimura; Son Anh Ho; Anh Hai Tran; Taketoshi Ono; Hisao Nishijo
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 985 KB
- Volume
- 17
- Category
- Article
- ISSN
- 1050-9631
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline due to neuronal loss and neural network dysfunction. It has been postulated that progressive neuronal loss in AD is consequence of the neurotoxic properties of the amyloid‐β peptide (Aβ). In the present study, we investigated the effect of T‐817MA (1‐{3‐[2‐(1‐benzothiophen‐5‐yl)ethoxy] propyl}‐3‐azetidinol maleate), a newly synthesized neurotrophic compound, on place learning deficits in rats with hippocampal damages. To induce granule cell loss in the dentate gyrus (DG) of the hippocampus, Aβ (1–40) was continuously infused (300 pmol/day) into the cerebral ventricle using a mini‐osmotic pump for 5 weeks. Three weeks after the Aβ infusion, the rats were tested in a place learning task, which required them to alternatively visit two diametrically opposed areas in an open field to obtain intracranial self‐stimulation reward. The results indicated that the Aβ‐infused rats without treatment of T‐817MA displayed learning impairment in the task; their performance level was significantly inferior to that of the vehicle rats. Treatment of T‐817MA (8.4 mg/kg/day, p.o.) significantly improved the task performance of the Aβ‐infused rats. Furthermore, T‐817MA prevented granule cell loss due to Aβ‐infusion, which was correlated to task performance of the rats. However, other cognitive enhancer, an acetylcholinesterase inhibitor, had no such effects. The results demonstrated that T‐817MA ameliorated learning deficits induced by Aβ infusion, which might be attributed to neuroprotection in the hippocampus. © 2007 Wiley‐Liss, Inc.