ArticleCell reports2019
Reconstitution of the Human Nigro-striatal Pathway on-a-Chip Reveals OPA1-Dependent Mitochondrial Defects and Loss of Dopaminergic Synapses.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Mitochondrial molecular diversity in the brain.Current opinion in neurobiology · 2026Review
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- Spatial and morphological organization of mitochondria in neurons across a connectome.Science (New York, N.Y.) · 2026Article
- Identification and experimental validation of biomarkers related to mitochondrial and programmed cell death in obsessive-compulsive disorder.Scientific reports · 2025Article
- The Use of Neurons Derived from Pluripotent Stem Cells to Study Nerve-Cancer Cell Interactions.International journal of molecular sciences · 2025Review
- Standardizing designed and emergent quantitative features in microphysiological systems.Nature biomedical engineering · 2024Review
- A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy.Lab on a chip · 2024Article
- Early deficits in an in vitro striatal microcircuit model carrying the Parkinson's GBA-N370S mutation.NPJ Parkinson's disease · 2024Article
- Microfluidic compartmentalization of rat vagal afferent neurons to model gut-brain axis.Bioelectronic medicine · 2024Article
- Micro/nanosystems for controllable drug delivery to the brain.Innovation (Cambridge (Mass.)) · 2024Review
- Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells.Nature communications · 2023Article
- Article
- Functional bioengineered tissue models of neurodegenerative diseases.Biomaterials · 2023Review
- Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections.Open biology · 2023Review
- Influence of microchannel geometry on device performance and electrophysiological recording fidelity during long-term studies of connected neural populations.Lab on a chip · 2022Article
- Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells.Human molecular genetics · 2022Article
- Levodopa Responsive Dystonia Parkinsonism, Intellectual Disability, and Optic Atrophy Due to a Heterozygous Missense Variant inMovement disorders clinical practice · 2022Article
- A Human Stem Cell-Derived Neurosensory-Epithelial Circuitry on a Chip to Model Herpes Simplex Virus Reactivation.Biomedicines · 2022Article
- Mitochondrial heterogeneity and homeostasis through the lens of a neuron.Nature metabolism · 2022Review
- Programming axonal mitochondrial maintenance and bioenergetics in neurodegeneration and regeneration.Neuron · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cell-derived neurons are generally obtained in mass cultures that lack both spatial organization and any meaningful connectivity. We implement a microfluidic system for long-term culture of human neurons with patterned projections and synaptic terminals. Co-culture of human midbrain dopaminergic and striatal medium spiny neurons on the microchip establishes an orchestrated nigro-striatal circuitry with functional dopaminergic synapses. We use this platform to dissect the mitochondrial dysfunctions associated with a genetic form of Parkinson's disease (PD) with OPA1 mutations. Remarkably, we find that axons of OPA1 mutant dopaminergic neurons exhibit a significant reduction of mitochondrial mass. This defect causes a significant loss of dopaminergic synapses, which worsens in long-term cultures. Therefore, PD-associated depletion of mitochondria at synapses might precede loss of neuronal connectivity and neurodegeneration. In vitro reconstitution of human circuitries by microfluidic technology offers a powerful system to study brain networks by establishing ordered neuronal compartments and correct synapse identity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.