Cited by 173Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

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Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice

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NELSON, R, GUO, Z, HALAGAPPA, V, PEARSON, M, GRAY, A, MATSUOKA, Y, BROWN, M, MARTIN, B, IYUN, T, MAUDSLEY, S·2007·Experimental Neurology

DOI 10.1016/j.expneurol.2007.01.037PMC PMC1979096

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Abstract

A history of depression is a risk factor for Alzheimer's disease (AD), suggesting the possibility that antidepressants administered prophylactically might retard the disease process and preserve cognitive function. Here we report that pre-symptomatic treatment with the antidepressant paroxetine attenuates the disease process and improves cognitive performance in the 3xTgAD mouse model of AD. Five-month-old male and female 3xTgAD and non-transgenic mice were administered either paroxetine or saline daily for 5 months. Open-field activity was tested in 7-month-old mice and performance in passive avoidance and Morris swim tasks were evaluated at 10 months. 3xTgAD mice exhibited reduced exploratory activity, increased transfer latency in the passive avoidance test and impaired performance in the Morris spatial navigation task compared to nontransgenic control mice. Paroxetine treatment ameliorated the spatial navigation deficit in 3xTgAD male and female mice, without affecting swim speed or distance traveled, suggesting a preservation of cognitive function. Levels of amyloid beta-peptide (Abeta) and numbers of Abeta immunoreactive neurons were significantly reduced in the hippocampus of male and female paroxetine-treated 3xTgAD mice compared to saline-treated 3xTgAD mice. Female 3xTgAD mice exhibited significantly less tau pathology in the hippocampus and amygdala compared to male 3xTgAD mice, and paroxetine lessened tau pathology in male 3xTgAD mice. The ability of a safe and effective antidepressant to suppress neuropathological changes and improve cognitive performance in a mouse model suggests that such drugs administered prophylactically might retard the development of AD in humans.

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Authors: NELSON, R., GUO, Z., HALAGAPPA, V, PEARSON, M., GRAY, A., MATSUOKA, Y., BROWN, M., MARTIN, B., IYUN, T., & MAUDSLEY, S.
Affiliations: Meharry Medical College (US)
National Institute on Aging (US)
Georgetown University (US)
ORCID: NELSON, R
MARTIN, B
MAUDSLEY, S
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2007-05
Volume: 205
Issue: 1
Pages: 166-176
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1016/j.expneurol.2007.01.037
PMC: PMC1979096
OpenAlex: W2114092053
Cited by: 173
References: 108
Citations by year: 2026: 2 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 16
FWCI: 7.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (Z01AG000312, AG022455, Z01AG000317, K01AG022455)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Keywords: paroxetine, Alzheimer's disease, 3xTg-AD mice, amyloid-beta, tau pathology, cognitive impairment, spatial navigation, hippocampus, amygdala, sex differences, depression as risk factor, behavioral deficits
MeSH terms: Alzheimer Disease, Amygdala, Animals, Avoidance Learning, Behavior, Animal, Mental Disorders, Cerebral Cortex, Disease Models, Animal, Female, Hippocampus, Male, Mice, Transgenic, Motor Activity, Peptide Fragments, Swimming, Amyloid beta-Peptides, Selective Serotonin Reuptake Inhibitors, Paroxetine, Maze Learning, Tauopathies, Mice

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Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice

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