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Abstract
Background: The pathophysiology of Parkinson's Disease (PD) can be attributed to a gradually progressive dopaminergic neuron (DN) degeneration and aggregation of abnormal α-synuclein in the basal ganglia. While the classic paradigm of PD focuses on the role of neurotransmitter imbalance and motor impairments, there has been increasing scientific interest in the link between the intricate connection between gut dysbiosis with synucleinopathies and PD. This review explores the relevance of the Braak hypothesis, short-chain fatty acids (SCFAs) in neuronal viability, and gastrointestinal barrier dysfunction through the lens of in vitro modeling.
Methods: A collection of prospective literature was conducted on the search engine PubMed to systematically look for in vitro models relating PD to gut-brain axis models. The search was limited to English-language articles from 1 January 2016–10 November 2024. Only in vitro experiments with relevance to the gut-brain axis or gastrointestinal organoids relating to PD were chosen for inclusion. All assessments for eligibility were done in person. Initial discussion prioritized the identification of in vitro models that either (1) focused primarily on PD or (2) involved the gut-brain axis with neurodegenerative disease within the title and abstract.
Results: A total of 1090 records were identified from the database search, and no duplicates are found; based on the exclusion and inclusion criteria by full texts screening, a total of 7 studies is selected. Discussion of differences in cell type, interconnections between organoid chips, method of measurement and detection, and overall structures and design of the in vitro models was made and tabulated. Multiculture models (n=4) utilized [e.g., HepG2, Caco-2, AHPC] cells to evaluate MPP+ neurotoxin, 5-HT epithelial secretion, and overall disease study typically via toxin or neurotransmitter attenuation as a control. Monoculture models (n=3) introduce rat progenitor cell lines or astrocyte cells to make direct measurements of gut epithelium and brain cells in PD. Organ-on-chip models (n=11) demonstrated 2D and 3D platform modeling to stimulate DN function, neuroinflammation, blood-brain integrity, and α-synuclein pathology. These models incorporate advanced features such as vascularization, microfluidics, multisensor integration, and real-time neuronal activity monitoring, supporting applications in disease modeling and drug screening.
Conclusions: In vitro models allow simulation of human biological processes in a controlled environment, and therefore offer a promising, scalable avenue of PD research where specific pathophysiological mechanisms, systemic interactions, and feedback mechanisms may be explored. However, these models are not without limitation. Multisection chip models, while working in series as sequential passages of cell cultures, still cannot mimic systemic factors and key body elements. We hope that as more challenges in developing complex in vitro systems become solved, the integration of additional organ systems will enable multi-organ frameworks to more accurately replicate the interactions underlying Parkinson’s disease pathophysiology.
Presentation Type
Poster
Recommended Citation
Cauba, John Nicholas; Woo, Jihoo; Wiggins, Russell; and Mito, Shizue, "Comprehensive Review of In Vitro Gut-Brain Axis Models in Parkinson’s Disease Research" (2025). Research Colloquium. 51.
https://scholarworks.utrgv.edu/colloquium/2025/posters/51
Included in
Comprehensive Review of In Vitro Gut-Brain Axis Models in Parkinson’s Disease Research
Background: The pathophysiology of Parkinson's Disease (PD) can be attributed to a gradually progressive dopaminergic neuron (DN) degeneration and aggregation of abnormal α-synuclein in the basal ganglia. While the classic paradigm of PD focuses on the role of neurotransmitter imbalance and motor impairments, there has been increasing scientific interest in the link between the intricate connection between gut dysbiosis with synucleinopathies and PD. This review explores the relevance of the Braak hypothesis, short-chain fatty acids (SCFAs) in neuronal viability, and gastrointestinal barrier dysfunction through the lens of in vitro modeling.
Methods: A collection of prospective literature was conducted on the search engine PubMed to systematically look for in vitro models relating PD to gut-brain axis models. The search was limited to English-language articles from 1 January 2016–10 November 2024. Only in vitro experiments with relevance to the gut-brain axis or gastrointestinal organoids relating to PD were chosen for inclusion. All assessments for eligibility were done in person. Initial discussion prioritized the identification of in vitro models that either (1) focused primarily on PD or (2) involved the gut-brain axis with neurodegenerative disease within the title and abstract.
Results: A total of 1090 records were identified from the database search, and no duplicates are found; based on the exclusion and inclusion criteria by full texts screening, a total of 7 studies is selected. Discussion of differences in cell type, interconnections between organoid chips, method of measurement and detection, and overall structures and design of the in vitro models was made and tabulated. Multiculture models (n=4) utilized [e.g., HepG2, Caco-2, AHPC] cells to evaluate MPP+ neurotoxin, 5-HT epithelial secretion, and overall disease study typically via toxin or neurotransmitter attenuation as a control. Monoculture models (n=3) introduce rat progenitor cell lines or astrocyte cells to make direct measurements of gut epithelium and brain cells in PD. Organ-on-chip models (n=11) demonstrated 2D and 3D platform modeling to stimulate DN function, neuroinflammation, blood-brain integrity, and α-synuclein pathology. These models incorporate advanced features such as vascularization, microfluidics, multisensor integration, and real-time neuronal activity monitoring, supporting applications in disease modeling and drug screening.
Conclusions: In vitro models allow simulation of human biological processes in a controlled environment, and therefore offer a promising, scalable avenue of PD research where specific pathophysiological mechanisms, systemic interactions, and feedback mechanisms may be explored. However, these models are not without limitation. Multisection chip models, while working in series as sequential passages of cell cultures, still cannot mimic systemic factors and key body elements. We hope that as more challenges in developing complex in vitro systems become solved, the integration of additional organ systems will enable multi-organ frameworks to more accurately replicate the interactions underlying Parkinson’s disease pathophysiology.
