ArticleEnvironmental health perspectives2022
Role of OCT3 and DRP1 in the Transport of Paraquat in Astrocytes: A Mouse Study.
Article in Environmental health perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 10 citations in OpenAlex.
- Chronic Paraquat Neurotoxicity and Dopaminergic Degeneration: A Mechanistic Review.Chemistry & biodiversity · 2026Review
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Soil to Synapse: Molecular Insights into the Neurotoxicity of Common Gardening Chemicals in Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2025Review
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Authors and funding
9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundParaquat (PQ) is a pesticide, exposure to which has been associated with an increased risk of Parkinson's disease; however, PQ transport mechanisms in the brain are still unclear. Our previous studies indicated that the organic cation transporter 3 (OCT3) expressed on astrocytes could uptake PQ and protect the dopaminergic (DA) neurons from a higher level of extracellular PQ. At present, it is unknown how OCT3 levels are altered during chronic PQ exposure or aging, nor is it clear how the compensatory mechanisms are triggered by OCT3 deficiency. Dynamic related protein 1 (DRP1) was previously reported to ameliorate the loss of neurons during Parkinson's disease. Nowadays, mounting studies have revealed the functions of astrocyte DRP1, prompting us to hypothesize that DRP1 could regulate the PQ transport capacity of astrocytes.
objectivesThe present study aimed to further explore PQ transport mechanisms in the nigrostriatal system and identify pathways involved in extracellular PQ clearance.
methodsModels of PQ-induced neurodegeneration were established by intraperitoneal (i.p.) injection of PQ in wild-type (WT) and organic cation transporter-3-deficient (
resultsOlder mice and those chronically exposed to PQ had a lower expression of brain OCT3 and, following exposure to a DISCUSSION: The present study mainly focused on the transport mechanisms of PQ between the dopaminergic neurons and astrocytes. Lower OCT3 levels were found in the older or chronically PQ-treated mice. Astrocytes with DRP1 inhibition (by viral tools or mitochondrial division inhibitor-1) had higher levels of ASCT2, which we hypothesize served as an alternative transporter to remove extracellular PQ when OCT3 was deficient. In summary, our data suggest that OCT3, ASCT2 located on astrocytes and the dopamine transporter located on DA terminals may function in a concerted manner to mediate striatal DA terminal damage in PQ-induced neurotoxicity. https://doi.org/10.1289/EHP9505.
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