Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling
| Autor: | Yunpeng Liu, Yu-Kang Mao, Karen-Anne McVey Neufeld, Paul Forsythe, Kevin Champagne-Jorgensen, Aadil Bharwani, Wolfgang Kunze, Michael G. Surette, John Bienenstock, Christine West |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Serotonin lcsh:Medicine Administration Oral Stimulation Pharmacology Gut flora Article Enteric Nervous System 03 medical and health sciences Mice 0302 clinical medicine Medicine Animals Neurons Afferent lcsh:Science Myenteric plexus Mice Inbred BALB C Multidisciplinary Excitability biology business.industry Depression lcsh:R digestive oral and skin physiology Brain Vagus Nerve biology.organism_classification Vagus nerve Gut Epithelium 030104 developmental biology Enteric nervous system lcsh:Q Reuptake inhibitor business Digestive System 030217 neurology & neurosurgery Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2045-2322 |
| Popis: | The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation. |
| Databáze: | OpenAIRE |
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