An in vitro multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins

Jones, Emily J.; Skinner, Benjamin M.; Parker, Aimee; Baldwin, Lydia R.; Greenman, John; Carding, Simon R.; Funnell, Simon G.P.

Abstract

The death of dopamine-producing neurons in the substantia nigra in the base of the brain is a defining pathological feature in the development of Parkinson's disease (PD). PD is, however, a multi-systemic disease, also affecting the peripheral nervous system and gastrointestinal tract (GIT) that interact via the gut-brain axis (GBA). Our dual-flow GIT-brain microphysiological system (MPS) was modified to investigate the gut-to-brain translocation of the neurotoxin trigger of PD, 1-methyl-4-phenylpyridinium (MPP+), and its impact on key GIT and brain cells that contribute to the GBA. The modular GIT-brain MPS in combination with quantitative and morphometric image analysis methods reproduces cell specific neurotoxin-induced dopaminergic cytotoxicity and mitochondria-toxicity with the drug having no detrimental impact on the viability or integrity of cellular membranes of GIT-derived colonic epithelial cells. Our findings demonstrate the utility and capability of the GIT-brain MPS for measuring neuronal responses and its suitability for identifying compounds or molecules produced in the GIT that can exacerbate or protect against neuronal inflammation and cell death.

Citation

Jones, E. J., Skinner, B. M., Parker, A., Baldwin, L. R., Greenman, J., Carding, S. R., & Funnell, S. G. (2024). An in vitro multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins. Biomicrofluidics, 18(5), Article 054105. https://doi.org/10.1063/5.0200459

• Journal Article Type: Article
• Acceptance Date: Aug 19, 2024
• Online Publication Date: Sep 13, 2024
• Publication Date: Sep 1, 2024
• Deposit Date: Sep 28, 2024
• Publicly Available Date: Oct 1, 2024
• Journal: Biomicrofluidics
• Electronic ISSN: 1932-1058
• Publisher: American Institute of Physics
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: 5
• Article Number: 054105
• DOI: https://doi.org/10.1063/5.0200459
• Keywords: Microfluidics; Optical imaging; Peripheral nervous system; Diseases and conditions; Cytotoxicity; Epithelial cells; Inflammation; Gastrointestinal tract; Cell membranes; Neuroanatomy
• Public URL: https://hull-repository.worktribe.com/output/4836438