Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability.

Autor: Du W; Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, Shandong, 266071, China., Chen H; Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, Shandong, 266071, China., Gróf I; Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary., Lemaitre L; Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary., Bocsik A; Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary., Perdyan A; 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, 80-210, Poland., Mieczkowski J; 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, 80-210, Poland., Deli MA; Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary., Hortobágyi T; Centre for Healthy Brain Ageing, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.; Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Wan Q; Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao, Shandong, 266071, China., Glebov OO; Centre for Healthy Brain Ageing, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. oleg.glebov@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Nov; Vol. 29 (11), pp. 3590-3598. Date of Electronic Publication: 2024 May 30.
DOI: 10.1038/s41380-024-02626-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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