Abstract
BackgroundNeuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.MethodsTo investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old.ResultsOur results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice.ConclusionOur data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.
Highlights
Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD
Paroxetine ameliorates emotional dysfunction in earlyage APP/PS1 mice At early stage of AD and related dementia, the symptoms of depression, anxiety, apathy, and irritability occur in prodromal phases of clinical disease
We performed transcriptional analysis of prefrontal cortex from AD patients to determine whether the expression of serotonergic (5-HTergic) system was changed compared with normal human
Summary
Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. AD is accompanied by synaptic loss, deposition of Aβ plaques, neurofibrillary tangles (NFTs), and hyperphosphorylated tau [3] These changes are developed progressively which results in AD pathology in the late period [4, 5]. Mild behavioral impairment patients without cognitive symptoms are more likely to develop dementia [10, 11], and those with MCI progress to AD at a much higher rate if they have NPS [12], indicating a history of depression or anxiety confer an increased risk for later developing AD [13]
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