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Protective effects of compound FLZ on -amyloid peptide-(25–35)-induced mouse hippocampal injury and learning and memory impairment

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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 (A25–35) in mice. Methods: Mice were icv injected with the A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 A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 A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 A25–35. Conclusion: FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of A25–35 in mice.
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Keywords: A25–35; Bax; Bcl-2; FLZ; acetylcholinesterase; hippocampus; intracerebroventricular injection; malondialdehyde

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

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