Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 36, Pages 14968-14973Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1107411108
Keywords
microdialysis; selective serotonin reuptake inhibitor antidepressants; late-life depression
Categories
Funding
- National Institutes of Health [K01 AG029524, R21 MH77124, K24 MHO79510]
- National Institute on Aging [P50 AG05681]
- National Institute of Neurological Disorders and Stroke [P30 NS069329, P01 AG03991]
- Charles F. and Joanne Knight Aging and Disability Resource Center at Washington University
- McDonnell Center for Cell and Molecular Biology
- Shmerler family
Ask authors/readers for more resources
Aggregation of amyloid-beta (A beta) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce A beta levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate A beta metabolism. We assessed the ability of serotonin signaling to alter brain A beta levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) A beta levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF A beta levels. Serotonin-dependent reductions in A beta were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact A beta plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less A beta accumulation in cognitively normal individuals.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available