Effect Of Fluoxetine On The Cholinergic Neurotransmitterr And Cholinergic Neurons In The Basal Forebrain Of Aged APP/PS1 Double Transgenic Mice

Fluoxetine is one of the most commonly antidepressants.While the effects of fluoxetine on cognitive and memory ability of AD patients are firmly established,debate about the specific mechanism underlying the effect of fuoxetine on AD is ongoing.To study whether the cholinergic system is one of the targets through which fluoxeitne improved the spatial learning and memory abilities in patients with AD,18-month-old male transgenic APP/PS1 mice(Tg +)as postive group(n = 20)and fluoxetine group(n = 20)and 18-month-old male non-transgenic mice(Tg-)as negative group(n = 20)were selected randomly in the current study.The spatial learning and memory ability of all mice were measured using Morris water maze.Meanwhile,the contents of Ach,the activity of Ch AT and Ach E were measured.Then the amyloid deposition was compared using immunohistochemical staining,and the total number of cholinergic neurons within basal forebrain were estimated using the stereological methods.We found that fluoxetine significantly improved the spatial learning ability of 18-month-old APP/PS1 mice.In addition,fluoxetine could reduce the amyloid deposition in the hippocampus of APP/PS1 mice and increase the contents of Ach and the activity of Ach E.However,fluoxetine had no obvious effect on the total number of cholinergic neurons within basal forebrain.Therefore,our current results suggested that fluoxetine could improve the spatial learning ability of APP/PS1 micethrough acting on the cholinergic system of AD brain.