Changes in Dendritic Spine Density and Morphology during Therapy with Acetylcholinesterase Inhibitors in a Mouse Model of Alzheimer's Disease.

We performed a comparative study of the effect of a new acetylcholinesterase inhibitor 1,3-bis[5-(o-nitrobenzylethylamino)pentyl]-6-methyluracil (C-35) and a commercial drug donepezil on the density and morphology of dendritic spines in the entorhinal cortex of transgenic APP/PS1 mice with a model of Alzheimer's disease. Administration of donepezil to transgenic mice did not significantly change spine density or morphology. In contrast, treatment with C-35 increased dendritic spine density by 56 and 34% in comparison with donepezil and the control group (untreated transgenic mice), respectively. This effect of C-35 was associated with an increase in the number of thin spines and a decrease number of stubby spines.