Background:
Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated
with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve
cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the
hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate
stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction.
Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice.
Objective:
In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus
of middle-aged APP/PS1 mice.
Results:
It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus
were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation
of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in
the hippocampus.
Conclusion:
These results indicated that the enhanced learning ability observed in FLX-treated middle-aged
APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by
FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late
stage.
Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk