@article{bibcite_4836, author = {Emily J. Jones and Benjamin M. Skinner and Aimee Parker and Lydia R. Baldwin and John Greenman and Simon R. Carding and Simon G. P. Funnell}, title = {An in vitro multi-organ microphysiological system (MPS) to investigate the gut-to-brain translocation of neurotoxins}, 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{\textquoteright}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{\textendash}brain axis (GBA). Our dual-flow GIT{\textendash}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{\textendash}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.}, year = {2024}, journal = {Biomicrofluidics}, volume = {18}, pages = {054105}, month = {2024-09-13}, issn = {1932-1058}, url = {https://doi.org/10.1063/5.0200459}, doi = {10.1063/5.0200459}, }