Protective effects of compound FLZ on beta-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment.
OBJECTIVE
To study the protective effects of compound FLZ, a novel synthetic analogue of natural squamosamide, on learning and memory impairment and lesions of the hippocampus caused by icv injection of beta-amyloid(25-35)(Abeta(25-35)) in mice.


METHODS
Mice were icv injected with the Abeta(25-35) (15 nmol/mouse), and then treated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16 consecutive days. The impairment of learning and memory in mice were tested using step-down test and Morris water maze test. The content of malondialdehyde (MDA) and the expressions of acetylcholinesterase (AChE), Bax, and Bcl-2 in the CA1 region of the mouse hippocampus were measured by biochemical and immunohistochemical analysis, respectively. The pathological damages of hippocampus were observed using a microscope.


RESULTS
FLZ (75 mg/kg, 150 mg/kg) significantly attenuated Abeta(25-35)-induced impairment of learning and memory in the step-down test and Morris water maze test. FLZ also reduced pathological damages to the hippocampus induced by Abeta(25-35). Furthermore, FLZ prevented the increase of AChE and Bax, and the decrease of Bcl-2 immunoreactive cells in the CA1 region of the hippocampus, and reduced the increase of MDA content in the hippocampus in mice injected with Abeta(25-35).


CONCLUSIONS
FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of Abeta(25-35) in mice.
Fang
Fang
F
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Liu
Geng-Tao
GT
D000110:Acetylcholinesterase / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D044482:Benzeneacetamides / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments; D010636:Phenols / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D044482:Benzeneacetamides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; C084439:squamosamide; D008315:Malondialdehyde; D000110:Acetylcholinesterase