2006-01-12
Xu Z, Zheng H, Law SL, Dong So D, Han Y, Xue H.

Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, China.

Alzheimer's disease (AD) and related dementing disorders having cognitive manifestations represent an increasing threat to public health. In the present study, the effects of a memory enhancing NLPR tetra-peptide (MEP), huperzine A (Hup A), or a combination of the two on the cognitive abilities of brain-lesioned mice were evaluated and compared with tacrine in the passive avoidance and Y-water maze tests for the acquisition and retention aspects of cognitive functions. MEP at microg kg(-1) doses, and Hup A or tacrine at mg kg(-1) doses significantly reversed the cognition deficits induced by scopolamine. For acquisition ability, it was observed that mice administered with MEP (4.0 microg kg(-1)) spent less time escaping onto the platform in the water maze than those treated with tacrine (1.5 mg kg(-1)); whereas for memory retention, tacrine-administration resulted in a higher step-through latency in mice at the tested dose regime. In addition, co-administration of MEP (2.0 microg kg(-1)) and Hup A (0.1 mg kg(-1)) exhibited an additive effect resulting in considerable improvements in both acquisition and retention abilities of brain-lesioned mice. The results demonstrated that MEP was highly efficient in the rescue of cognitive abilities of brain-lesioned mice and in particular, the effective doses of MEP were about two orders of magnitude lower than that of tacrine, a therapeutic currently used in the treatment of AD. Moreover, MEP and Hup A were effective at reduced doses when the two were co-administered, providing a rationale for their combined usage in the treatment of cognitive deficits. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

PMID: 15942937 [PubMed - indexed for MEDLINE]