ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
VGLUT2 Is a Determinant of Dopamine Neuron Resilience in a Rotenone Model of Dopamine Neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- 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
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.Molecular psychiatry · 2025Article
- Parkinson's Disease-vulnerable and -resilient dopamine neurons display opposite responses to excitatory input.bioRxiv : the preprint server for biology · 2025Article
- Parallel Gene Expression Changes in Ventral Midbrain Dopamine and GABA Neurons during Normal Aging.eNeuro · 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
- 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
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.bioRxiv : the preprint server for biology · 2024Article
- Empagliflozin repurposing in Parkinson's disease; modulation of oxidative stress, neuroinflammation, AMPK/SIRT-1/PGC-1α, and wnt/β-catenin pathways.Inflammopharmacology · 2024Article
- Alterations in neurotransmitter co-release in Parkinson's disease.Experimental neurology · 2023Review
- Mitochondrial impairment and synaptic dysfunction are associated with neurological defects in iPSCs-derived cortical neurons of MERRF patients.Journal of biomedical science · 2023Article
- Development, wiring and function of dopamine neuron subtypes.Nature reviews. Neuroscience · 2023Review
- α-Synuclein in synaptic function and dysfunction.Trends in neurosciences · 2023Review
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- A mini-review of the role of vesicular glutamate transporters in Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Sex Differences in Dopaminergic Vulnerability to Environmental Toxicants - Implications for Parkinson's Disease.Current environmental health reports · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is characterized by progressive dopamine (DA) neuron loss in the SNc. In contrast, DA neurons in the VTA are relatively protected from neurodegeneration, but the underlying mechanisms for this resilience remain poorly understood. Recent work suggests that expression of the vesicular glutamate transporter 2 (VGLUT2) selectively impacts midbrain DA neuron vulnerability. We investigated whether altered DA neuron VGLUT2 expression determines neuronal resilience in rats exposed to rotenone, a mitochondrial complex I inhibitor and toxicant model of PD. We discovered that VTA/SNc DA neurons that expressed VGLUT2 are more resilient to rotenone-induced DA neurodegeneration. Surprisingly, the density of neurons with detectable VGLUT2 expression in the VTA and SNc increases in response to rotenone. Furthermore, dopaminergic terminals within the NAc, where the majority of VGLUT2-expressing DA neurons project, exhibit greater resilience compared with DA terminals in the caudate/putamen. More broadly, VGLUT2-expressing terminals are protected throughout the striatum from rotenone-induced degeneration. Together, our data demonstrate that a distinct subpopulation of VGLUT2-expressing DA neurons are relatively protected from rotenone neurotoxicity. Rotenone-induced upregulation of the glutamatergic machinery in VTA and SNc neurons and their projections may be part of a broader neuroprotective mechanism. These findings offer a putative new target for neuronal resilience that can be manipulated to prevent toxicant-induced DA neurodegeneration in PD.
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