Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 30.
doi: 10.1038/s41380-024-02626-1. Online ahead of print.

Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability

Wenjia Du  1 , Huanhuan Chen  1 , Ilona Gróf  2 , Lucien Lemaitre  2 , Alexandra Bocsik  2 , Adrian Perdyan  3 , Jakub Mieczkowski  3 , Mária A Deli  2 , Tibor Hortobágyi  4   5 , Qi Wan  1 , Oleg O Glebov  6
Affiliations

Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability

Wenjia Du et al. Mol Psychiatry. .

Abstract

As the most prescribed psychotropic drugs in current medical practice, antidepressant drugs (ADs) of the selective serotonin reuptake inhibitor (SSRI) class represent prime candidates for drug repurposing. The mechanisms underlying their mode of action, however, remain unclear. Here, we show that common SSRIs and selected representatives of other AD classes bidirectionally regulate fluid-phase uptake at therapeutic concentrations and below. We further characterize membrane trafficking induced by a canonical SSRI fluvoxamine to show that it involves enhancement of clathrin-mediated endocytosis, endosomal system, and exocytosis. RNA sequencing analysis showed few fluvoxamine-associated differences, consistent with the effect being independent of gene expression. Fluvoxamine-induced increase in membrane trafficking boosted transcytosis in cell-based blood-brain barrier models, while a single injection of fluvoxamine was sufficient to enable brain accumulation of a fluid-phase fluorescent tracer in vivo. These findings reveal modulation of membrane trafficking by ADs as a possible cellular mechanism of action and indicate their clinical repositioning potential for regulating drug delivery to the brain.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Burns C. Antidepressant prescribing increases by 35% in six years. Pharm J. 2022. https://pharmaceutical-journal.com/article/news/antidepressant-prescribi...
    1. Locher C, Koechlin H, Zion SR, Werner C, Pine DS, Kirsch I, et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74:1011–20. - PubMed - PMC - DOI
    1. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391:1357–66. - PubMed - PMC - DOI
    1. Ioannidis JP. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials? Philos Ethics Humanit Med. 2008;3:14. - PubMed - PMC - DOI
    1. Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2023;28:3243–56.

LinkOut - more resources

-