Protective effects of compound FLZ on -amyloid peptide-(25–35)-induced mouse hippocampal injury and learning and memory impairment
Aim: 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 -amyloid25–35 (A25–35) in mice. Methods: Mice were icv injected with the A25–35 (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 A25–35-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 A25–35. 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 A25–35. Conclusion: FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of A25–35 in mice.
Document Type: Research Article
Affiliations: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Publication date: 2006-06-01