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ToolsJones, Emily J., Skinner, Benjamin M., Parker, Aimee, Baldwin, Lydia R., Greenman, John, Carding, Simon R. and Funnell, Simon G. P. (2024) An in vitro multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins. Biomicrofluidics, 18 (5). ISSN 1932-1058
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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.
| Item Type: | Article |
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| Additional Information: | Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding Information: Under a collaborative agreement between the University of Essex, the University of Hull, the Quadram Institute Bioscience, and the UK Health Security Agency, funding was provided via the University of Essex's IAA Challenge Lab initiative 12288RC3302 (Public Health Challenge Lab, University of Essex via the Economic and Social Research Council) to the University of Hull and the Quadram Institute Bioscience through UKHSA. E.J.J., A.P., and S.R.C. were supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent projects under Nos. BBS/E/F/000PR10353, BBS/E/F/000PR10355, and BBS/E/F/000PR10346. B.S. was supported by the UKRI funding to the University of Essex. L.B. was funded by an Allam PhD studentship (University of Hull). The authors gratefully acknowledge the Quadram Institute Biosciences Advanced Microscopy Facility for their support and assistance in this work. |
| Uncontrolled Keywords: | biomedical engineering,materials science(all),condensed matter physics,fluid flow and transfer processes,colloid and surface chemistry ,/dk/atira/pure/subjectarea/asjc/2200/2204 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 25 Oct 2024 09:30 |
| Last Modified: | 25 Oct 2024 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97197 |
| DOI: | 10.1063/5.0200459 |
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