Acta Pharmacologica Sinica 2006 June; 27 (6): 651-658; doi: 10.1111/j.1745-7254.2006.00347.x

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 b-amyloid_25-35 (Ab_25-35) in mice.

Methods: Methods: Mice were icv injected with the Ab_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 Ab_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 Ab_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 Ab_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 Ab_25-35 in mice.

Keywords: FLZ; Ab_25-35; intracerebroventricular injec-tion; hippocampus; acetylcholinesterase; Bax; Bcl-2; malondialdehyde