In:
Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 19 ( 2020-11-10), p. e2666-e2674
Abstract:
Several neurotransmitter receptors activate signaling pathways that alter processing of the amyloid precursor protein (APP) into β-amyloid (Aβ). Serotonin signaling through a subset of serotonin receptors suppresses Aβ generation. We proposed that escitalopram, the most specific selective serotonin reuptake inhibitor (SSRI) that inhibits the serotonin transporter SERT, would suppress Aβ levels in mice. Objectives We hypothesized that acute treatment with escitalopram would reduce Aβ generation, which would be reflected chronically with a significant reduction in Aβ plaque load. Methods We performed in vivo microdialysis and in vivo 2-photon imaging to assess changes in brain interstitial fluid (ISF) Aβ and Aβ plaque size over time, respectively, in the APP/presenilin 1 mouse model of Alzheimer disease treated with vehicle or escitalopram. We also chronically treated mice with escitalopram to determine the effect on plaques histologically. Results Escitalopram acutely reduced ISF Aβ by 25% by increasing α-secretase cleavage of APP. Chronic administration of escitalopram significantly reduced plaque load by 28% and 34% at 2.5 and 5 mg/d, respectively. Escitalopram at 5 mg/kg did not remove existing plaques, but completely arrested individual plaque growth over time. Conclusions Escitalopram significantly reduced Aβ in mice, similar to previous findings in humans treated with acute dosing of an SSRI.
Type of Medium:
Online Resource
ISSN:
0028-3878
,
1526-632X
DOI:
10.1212/WNL.0000000000010733
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
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