Du, Wenjia and Chen, Huanhuan and Gróf, Ilona and Lemaitre, Lucien and Bocsik, Alexandra and Perdyan, Adrian and Mieczkowski, Jakub and Deli, Mária Anna and Hortobágyi, Tibor and Wan, Qi and Glebov, Oleg O. (2024) Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability. MOLECULAR PSYCHIATRY, 29. pp. 3590-3598. ISSN 1359-4184
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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.
| Item Type: | Article |
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| Additional Information: | Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Shandong, Qingdao, 266071, China Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, 80-210, Poland Centre for Healthy Brain Ageing, Department of Psychological Medicine, Institute of Psychiatry, Psychology & amp; Neuroscience, King’s College London, De Crespigny Park, London, SE5 8AF, United Kingdom Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Export Date: 19 June 2024 CODEN: MOPSF Correspondence Address: Glebov, O.O.; Centre for Healthy Brain Ageing, De Crespigny Park, United Kingdom; email: oleg.glebov@kcl.ac.uk Funding details: 2017-1.2.1-NKP-2017-00002 Funding details: 1G3DBLJ0TUDF 247 Funding details: National Natural Science Foundation of China, NSFC, 32070772 Funding details: National Natural Science Foundation of China, NSFC Funding details: OOG2019/2020 Funding details: Magyar Tudományos Akadémia, MTA, NAP2022-I-6/2022 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: This work was funded by the Lewy Body Society (OOG2019/2020), the National Natural Science Foundation of China (32070772), Hungarian Academy of Sciences (NAP2022-I-6/2022) Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002), and University of Debrecen Research Support Fund (1G3DBLJ0TUDF 247). |
| Subjects: | R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 24 Jan 2025 12:10 |
| Last Modified: | 24 Jan 2025 12:10 |
| URI: | https://real.mtak.hu/id/eprint/214325 |
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