ArticleBrain : a journal of neurology2022
Dopamine neurons exhibit emergent glutamatergic identity in Parkinson's disease.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- VGLUT2 in Parkinson's disease: an emerging therapeutic target.Expert opinion on therapeutic targets · 2026Review
- The Vesicular Glutamate Transporter Modulates Sex and Region-Specific Differences in Dopaminergic Neuron α-Synuclein Toxicity by Modifying Cytosolic Dopamine Levels.bioRxiv : the preprint server for biology · 2026Article
- dVGLUT Is a Mediator of Sex Differences in Dopamine Neuron Mitochondrial Function Across Aging and in a Parkinson's Disease Model.Aging cell · 2025Article
- Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.bioRxiv : the preprint server for biology · 2025Article
- Parkinson's Disease-vulnerable and -resilient dopamine neurons display opposite responses to excitatory input.bioRxiv : the preprint server for biology · 2025Article
- Translating stress systems: corticotropin releasing factor, its receptors, and the dopamine system in nonhuman primate models.Genomic psychiatry : advancing science from genes to society · 2025Article
- Parkinson disease-associated toxic exposures selectively up-regulate vesicular glutamate transporter vGlut2 in a model of human cortical neurons.Molecular biology of the cell · 2025Article
- Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.CNS & neurological disorders drug targets · 2025Review
- Single-Cell Nuclear Sequencing Atlas Revealed the Induction of Parkinson's Disease by RELN+ Neuron 3 and the Gene Regulatory Network of MSRA.Current medicinal chemistry · 2025Article
- Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.Therapeutic advances in neurological disorders · 2025Review
- Dopamine-Glutamate and Dopamine-GABA Co-release.Advances in neurobiology · 2025Review
- Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta.Addiction neuroscience · 2024Article
- Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies.Frontiers in integrative neuroscience · 2024Review
- Alterations in neurotransmitter co-release in Parkinson's disease.Experimental neurology · 2023Review
- Unique functional responses differentially map onto genetic subtypes of dopamine neurons.Nature neuroscience · 2023Article
- Dopamine and vesicular monoamine transport loss supports incidental Lewy body disease as preclinical idiopathic Parkinson.NPJ Parkinson's disease · 2023Article
- α-Synuclein in synaptic function and dysfunction.Trends in neurosciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss of midbrain dopamine neurons causes the cardinal symptoms of Parkinson's disease. However, not all dopamine neurons are equally vulnerable and a better understanding of the cell-type specific properties relating to selective dopamine neuron degeneration is needed. Most midbrain dopamine neurons express the vesicular glutamate transporter VGLUT2 during development and a subset continue to express low levels of VGLUT2 in adulthood, enabling the co-release of glutamate. Moreover, VGLUT2 expression in dopamine neurons can be neuroprotective since its genetic disruption was shown to sensitize dopamine neurons to neurotoxins. Here, we show that in response to toxic insult, and in two distinct models of alpha-synuclein stress, VGLUT2 dopamine neurons were resilient to degeneration. Dopamine neurons expressing VGLUT2 were enriched whether or not insult induced dopamine neuron loss, suggesting that while VGLUT2 dopamine neurons are more resilient, VGLUT2 expression can also be transcriptionally upregulated by injury. Finally, we observed that VGLUT2 expression was enhanced in surviving dopamine neurons from post-mortem Parkinson's disease individuals. These data indicate that emergence of a glutamatergic identity in dopamine neurons may be part of a neuroprotective response in Parkinson's disease.
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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.