Protective effects of compound FLZ onβ-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 ana- logue of natural squamosamide,on learning and memory impairment and lesions of the hippocampus caused by icv injection of β-amyloid_(25-35)(Aβ_(25-35))in mice. Methods:Mice were icv injected with the Aβ_(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 immu- nohistochemical analysis,respectively.The pathological damages of hippocam- pus were observed using a microscope.Results:FLZ(75 mg/kg,150 mg/kg) significantly attenuated Aβ_(25-35)-induced impairment of learning and memory in the step-down test and Morris water maze test.FLZ also reduced pathological dam- ages to the hippocampus induced by Aβ_(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 Aβ_(25-35).Conclusion:FLZ has protective ac- tion against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of Aβ_(25-35)in mice.