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Ameliorative effects of a neuroprotective agent, T‐817MA, on place learning deficits induced by continuous infusion of amyloid‐β peptide (1–40) in rats
Author(s) -
Nguyen Phuong Thi Hong,
Kimura Tatsuo,
Ho Son Anh,
Tran Anh Hai,
Ono Taketoshi,
Nishijo Hisao
Publication year - 2007
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20281
Subject(s) - dentate gyrus , neuroprotection , hippocampal formation , hippocampus , neuroscience , psychology , granule cell , medicine , neurotrophic factors , endocrinology , pharmacology , chemistry , receptor
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.