Abstract
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer’s disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.
Highlights
Alzheimer’s disease (AD) has emerged as the most common cause of dementia in the elderly, characterized by progressive learning dysfunction and memory loss
To investigate whether FLX treatment prevents impairments in learning and memory abilities in AD mice, three groups of mice were subjected to the Morris water maze, which is a well-known test for evaluating hippocampus-dependent learning and memory
The health of the mice was closely supervised, and the body weights of the mice were measured daily during treatment
Summary
Alzheimer’s disease (AD) has emerged as the most common cause of dementia in the elderly, characterized by progressive learning dysfunction and memory loss. Amyloid deposits and neurofibrillary tangles, two main pathological hallmarks of AD in the hippocampus, have been found to result in significant hippocampal neuronal dysfunction and death in the clinically detectable stage of AD [2,3,4]. It has been reported that the decline in cognitive abilities during the late stage of AD appears to more correlate with significant neuron loss than with the amyloid deposits and neurofibrillary tangles in the hippocampus [1, 7, 8]. Several drugs have been approved for the clinical treatment of AD [13], these drugs activate cholinergic or suppress glutamatergic neurotransmission and improve only the symptoms of AD Their neuroprotective activities remain a topic of debate [14,15,16]
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