ArticleProceedings of the National Academy of Sciences of the United States of America2018
Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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40 citing papers in PubMed, 61 citations in OpenAlex.
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 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
- 5-HT2C receptors in the glutamatergic neurons of dorsal raphe nucleus orchestrate the comorbidity of pain and anxiety in mice.BMC medicine · 2026Article
- Article
- Two classes of amine/glutamate multi-transmitter neurons innervate Drosophila internal male reproductive organs.bioRxiv : the preprint server for biology · 2025Article
- 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
- Article
- 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
- Molecular heterogeneity and development of the ventral tegmental area.Current opinion in behavioral sciences · 2025Article
- Single-Cell Profiling Identifies Reward Behavior-Related Neurons and Alterations in the Ventral Tegmental Area Based onResearch (Washington, D.C.) · 2025Article
- 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
- Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.Neuropharmacology · 2024Article
- Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases.Nature reviews. Neuroscience · 2024Review
- Alterations in neurotransmitter co-release in Parkinson's disease.Experimental neurology · 2023Review
- Modeling methamphetamine use disorder and relapse in animals: short- and long-term epigenetic, transcriptional., and biochemical consequences in the rat brain.Neuroscience and biobehavioral reviews · 2023Review
- Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity.Science advances · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A subset of midbrain dopamine (DA) neurons express vesicular glutamate transporter 2 (VgluT2), which facilitates synaptic vesicle loading of glutamate. Recent studies indicate that such expression can modulate DA-dependent reward behaviors, but little is known about functional consequences of DA neuron VgluT2 expression in neurodegenerative diseases like Parkinson's disease (PD). Here, we report that selective deletion of VgluT2 in DA neurons in conditional VgluT2-KO (VgluT2-cKO) mice abolished glutamate release from DA neurons, reduced their expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB), and exacerbated the pathological effects of exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, viral rescue of VgluT2 expression in DA neurons of VglutT2-cKO mice restored BDNF/TrkB expression and attenuated MPTP-induced DA neuron loss and locomotor impairment. Together, these findings indicate that VgluT2 expression in DA neurons is neuroprotective. Genetic or environmental factors causing reduced expression or function of VgluT2 in DA neurons may place some individuals at increased risk for DA neuron degeneration. Therefore, maintaining physiological expression and function of VgluT2 in DA neurons may represent a valid molecular target for the development of preventive therapeutic interventions for PD.
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