Effects of fluoxetine on cholinergic neurons in dentate gyrus of 8-month-old APP/PS1 mice: a stereological study

Abstract

Objective To investigate the change of the total number and density of cholinergic neurons in dentate gyrus (DG) of hippocampus of 8-month-old APP/PS1 mice after fluoxetine (FLX) intervention and analyze whether the improvement of cognitive function is related to the change of the number of cholinergic neurons after FLX intervention. Methods Twenty 8-month-old female APP/PS1 mice were randomly divided into control group and intervention group. The mice in the control group and the intervention group were given 8 weeks of normal saline and the same amount of FLX by intraperitoneal injection, Then, Morris water maze test was used to test the learning and memory ability of the mice. The total number and density of the cholinergic neurons in the DG were calculated using stereological methods. The cholinergic-related neurotransmitters were determined by enzyme-linked immunosorbent assay. Results The results of Morris water maze test showed that the escape latency of the intervention group was significantly shorter than that of the control group (P < 0.05). The results of stereological findings showed that FLX significantly increased the total number and density of cholinergic neurons in the DG of hippocampus of 8-month-old APP/PS1 mice (P < 0.01); The results of enzyme linked immunosorbent assay showed that FLX statistically increased the level of acetylcholine (ACh) in the hippocampus of APP/PS1 mice (P < 0.01). Conclusion The change of the total number of cholinergic neurons in the DG of hippocampus and the level of ACh in the hippocampus may be related to the behavioral changes of 8-month-old APP/PS1 mice after FLX intervention.

Keywords

• cholinergic neuron
• hippocampus
• fluoxetine
• stereology