Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice

Abstract

Background: 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. 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. Methods: To 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. Results: Our 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. Conclusion: Our 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.

Network-based stage-specific drug repurposing for Alzheimer’s disease

“…Of the top-15 candidate repurposed drugs in total, none of them have been tested in clinical trials for AD yet. However, drugs such as camptothecin, vinpocetine, paroxetine, naloxone and mepacrine have been tested in pre-clinical AD models [39] , [40] , [41] , [42] . Table 5 shows a summary of all the clinical trials that each candidate repurposed drug is involved.…”

EphB2 mediates social isolation-induced memory forgetting

“…Immunofluorescence was performed as described in our previous study 34 , coronal brain slices were blocked with permeable buffer (0.3% Triton X-100 in PBS) containing 10% donkey serum for 1 h at room temperature and were incubated with primary antibodies in permeable buffer containing 2% donkey serum overnight at 4°C. The slices were then washed three times with PBS-T (0.1% Tween-20 in PBS) for 10 min each and incubated with Alexa Fluor secondary antibodies (1:200; Molecular Probes) in the PBS buffer for 2 h at room temperature.…”

Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice

“…The preclinical phase of AD is designated as mild cognitive impairment (MCI), which is defined as the basis of an abnormal decline of cognition for age ( 4 ). Accumulating clinical and experimental evidence has shown that the pathogenic process starts decades before the clinical onset of AD ( 5 , 6 ). Patients with MCI progress to AD at an annual rate of 5% to 10% compared with 1% to 2% incidence per year among the general population ( 7 ).…”