ArticleThe Journal of clinical investigation2018
Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 106 citations in OpenAlex.
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 2026Review
- Selective and differential roles of PVHNature communications · 2026Article
- 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
- Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations.Genome research · 2025Article
- Article
- dVGLUT Is a Mediator of Sex Differences in Dopamine Neuron Mitochondrial Function Across Aging and in a Parkinson's Disease Model.Aging cell · 2025Article
- A ventral pallidal glutamatergic aversive network encodes abstinence from and reexposure to cocaine.Science advances · 2025Article
- Parkinson's paradox: alpha-synuclein's selective strike on SNc dopamine neurons over VTA.NPJ Parkinson's disease · 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
- Dopamine-Glutamate and Dopamine-GABA Co-release.Advances in neurobiology · 2025Review
- Extrinsic and intrinsic control of striatal cholinergic interneuron activity.Frontiers in molecular neuroscience · 2025Review
- Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta.Addiction neuroscience · 2024Article
- Molecular diversity and migration of GABAergic neurons in the developing ventral midbrain.iScience · 2024Article
- Human brain proteome-wide association study provides insights into the genetic components of protein abundance in obesity.International journal of obesity (2005) · 2024Article
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- Multiple cholinergic receptor subtypes coordinate dual modulation of acetylcholine on anterior and posterior paraventricular thalamic neurons.Journal of neurochemistry · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development.
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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.