Exploring Therapeutic Strategies for Neuropsychiatric Disorders: Modulating Inflammation, Gut-Brain Interactions, and the Role of Butyrate

• Published in: The Journal of pharmacology and experimental therapeutics 2024-06, Vol.389 (S3), p.336-336
• Main Authors: Vumma, Ravi, Rode, Julia, Yang, Lin, Montero, Jessica, Konig, Julia, Wall, Rebecca, Hutchinson, Ashley, Venizelos, Nikolaos, Brummer, Robert, Rangel, Ignacio
• Format: Article
• Language: English
• Subjects: Neuropsychiatric Disorders; Psychiatry; Psykiatri
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.336.127906

Abstract ID 127906 Poster Board 336 Neuropsychiatric disorders present significant challenges due to their complex etiology, involving inflammatory responses, neurotransmitter dysregulation, and altered gut-brain interactions. Recent interdisciplinary research uncovers the gut-brain axis (GBA), connecting the central and enteric nervous systems through various pathways. The intestinal microbiota, crucial to the GBA, impacts brain function via bacterial metabolic products like butyrate. This study addresses these complexities by examining the role of butyrate in modulating the influence of proinflammatory responses and oxidative stress on the transport of neurotransmitter precursor amino acids tyrosine and tryptophan and gene expression of these transporters. Fibroblasts derived from human skin obtained from a healthy control were used as model cells for the blood-brain barrier in this research project. Fibroblasts were treated with proinflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF- α) and oxidative stress (hydrogen peroxide) to assess the uptake of 14C tyrosine. Additionally, fibroblasts were treated with oxidative stress and different concentrations of butyrate to measure the transport of 3H tryptophan across the cell membranes. Furthermore, gene expression profiles in response to oxidative stress and butyrate treatment of tyrosine and tryptophan amino acid transporters were analyzed. Proinflammatory cytokines and oxidative stress were found to significantly decrease tyrosine transport. Oxidative stress significantly decreased tryptophan uptake, while butyrate counteracted this effect. However, treatment of oxidative stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tyrosine and tryptophan. In conclusion, this research project elucidated the pathophysiological mechanisms of proinflammatory responses in neuropsychiatric disorders. Moreover, it highlights the therapeutic potential of butyrate and emphasizes the significance of gut-brain interactions in these conditions. By shedding light on these aspects, this research contributes to the development of innovative and personalized treatment strategies for enhanced management of neuropsychiatric disorders.