Effects of a memory enhancing peptide on cognitive abilities of brain-lesioned mice: additivity with huperzine A and relative potency to tacrine.
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.
Xu
Zhiwen
Z
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, China.
Zheng
Hui
H
Law
Sek Lun
SL
Dong So
Donna
D
Han
Yifan
Y
Xue
Hong
H
D000470:Alkaloids; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001927:Brain Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D012601:Scopolamine / Q000737:chemistry; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D010446:Peptide Fragments; D012717:Sesquiterpenes; C050426:huperzine A; D013619:Tacrine; D012601:Scopolamine