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While cells in the human body function in an environment where the blood supply constantly delivers nutrients and removes waste, cells in conventional tissue culture well platforms are grown with a static pool of media above them and often lack maturity, limiting their utility to study cell biology in health and disease. In contrast, organ-chip microfluidic systems allow the growth of cells under constant flow, more akin to the in vivo situation. Here, we differentiated human induced pluripotent stem cells into dopamine neurons and assessed cellular properties in conventional multi-well cultures and organ-chips. We show that organ-chip cultures, compared to multi-well cultures, provide an overall greater proportion and homogeneity of dopaminergic neurons as well as increased levels of maturation markers. These organ-chips are an ideal platform to study mature dopamine neurons to better understand their biology in health and ultimately in neurological disorders.
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http://dx.doi.org/10.3390/ijms241814227 | DOI Listing |
Brain
September 2025
Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan.
Animal models of the pathology of Parkinson's disease (PD) have provided most of the treatments to date, but the disease is restricted to human patients. In vitro models using human pluripotent stem cells (hPSCs)-derived neural organoids have provided improved access to study PD etiology. This study established a method to generate human striatal-midbrain assembloids (hSMAs) from hPSCs for modeling alpha-synuclein (α-syn) propagation and recapitulating basal ganglia circuits, including nigrostriatal and striatonigral pathways.
View Article and Find Full Text PDFIBRO Neurosci Rep
December 2025
Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
Objective: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized pathologically by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a significant decline in striatal dopamine levels. This study aims to systematically analyze alterations in striatal metabolites across different stages of PD to identify potential biomarkers, elucidate pathological mechanisms, and explore therapeutic targets.
Methods: A total of 72 mice were divided into six groups, including one control group and five PD model groups (W1-W5, representing distinct stages based on the duration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid induction).
Front Biosci (Landmark Ed)
August 2025
Division of Life Sciences and Department of Life Science, Graduate School, CHA University, 13488 Seongnam-si, Gyeonggi-do, Republic of Korea.
Background: Parkinson's disease (PD) is characterized by a progressive decline in dopaminergic neurons within the substantia nigra (SN). Although its underlying cause has yet to be fully elucidated, accumulating evidence suggests that neuroinflammation contributes substantially to disease development. Treatment strategies targeting neuroinflammation could improve PD outcomes.
View Article and Find Full Text PDFEur J Pharmacol
September 2025
Faculty of Medicine, Department of Histology and Embryology, İzmir Katip Çelebi University, İzmir, Turkiye.
Age is the most significant risk factor for Parkinson's disease, a common and progressive neurodegenerative disorder; however, exposure to toxic substances is also strongly implicated. Rotenone, an organic pesticide, induces neuropathological features of Parkinson's disease, and is widely used to create rodent models of the condition. Although the molecular mechanisms involved in the onset and progression of the disease are still unknown, neurodegenerative diseases due to protein accumulation in certain areas of the brain, have been associated with endoplasmic reticulum stress.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AB, UK.
Disrupted gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of schizophrenia. Reductions in hippocampal GABAergic neurons have been found in schizophrenia, and increased hippocampal perfusion has been described in schizophrenia and in people at clinical high-risk for psychosis (CHRp). We have also found decreases in hippocampal GABA receptors containing the α5 subunit (GABARα5) in a well-validated neurodevelopmental rat model of relevance for schizophrenia.
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