ArticleNeurobiology of disease2011
Increased vesicular glutamate transporter expression causes excitotoxic neurodegeneration.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- 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
- Review of neuroprotective potential of natural products against hypoxia-induced neuronal injury.Frontiers in pharmacology · 2026Review
- Reactive Astrocytes Release GDNF to Promote Brain Recovery and Neuronal Survival Following Ischemic Stroke.Neurochemical research · 2025Article
- Microglia and Immune cells interactions in multiple sclerosis cognitive impairment: a postmortem study.Journal of neuroinflammation · 2024Article
- Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome.Scientific reports · 2024Article
- Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats.Biomolecules · 2024Article
- Article
- Pathological Interplay between Inflammation and Mitochondria Aggravates Glutamate Toxicity.International journal of molecular sciences · 2024Review
- Article
- Inhibition of Vesicular Glutamate Transporters (VGLUTs) with Chicago Sky Blue 6B Before Focal Cerebral Ischemia Offers Neuroprotection.Molecular neurobiology · 2023Article
- Autocrine inhibition by a glutamate-gated chloride channel mediates presynaptic homeostatic depression.Science advances · 2021Article
- Metabolic flux from the Krebs cycle to glutamate transmission tunes a neural brake on seizure onset.PLoS genetics · 2021Article
- Synaptic homeostats: latent plasticity revealed at the Drosophila neuromuscular junction.Cellular and molecular life sciences : CMLS · 2021Review
- Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling.PLoS genetics · 2021Article
- Glutamic Acid Transporters: Targets for Neuroprotective Therapies in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Vesicular neurotransmitter transporters in Drosophila melanogaster.Biochimica et biophysica acta. Biomembranes · 2020Review
- Histone Deacetylase 4 Downregulation Elicits Post-Traumatic Psychiatric Disorders through Impairment of Neurogenesis.Journal of neurotrauma · 2019Article
- Diet-induced insulin resistance elevates hippocampal glutamate as well as VGLUT1 and GFAP expression in AβPP/PS1 mice.Journal of neurochemistry · 2019Article
- Upregulation of Vesicular Glutamate Transporter 2 and STAT3 Activation in the Spinal Cord of Mice Receiving 3,3'-Iminodipropionitrile.Neurotoxicity research · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Increases in vesicular glutamate transporter (VGLUT) levels are observed after a variety of insults including hypoxic injury, stress, methamphetamine treatment, and in genetic seizure models. Such overexpression can cause an increase in the amount of glutamate released from each vesicle, but it is unknown whether this is sufficient to induce excitotoxic neurodegeneration. Here we show that overexpression of the Drosophila vesicular glutamate transporter (DVGLUT) leads to excess glutamate release, with some vesicles releasing several times the normal amount of glutamate. Increased DVGLUT expression also leads to an age-dependent loss of motor function and shortened lifespan, accompanied by a progressive neurodegeneration in the postsynaptic targets of the DVGLUT-overexpressing neurons. The early onset lethality, behavioral deficits, and neuronal pathology require overexpression of a functional DVGLUT transgene. Thus overexpression of DVGLUT is sufficient to generate excitotoxic neuropathological phenotypes and therefore reducing VGLUT levels after nervous system injury or stress may mitigate further damage.
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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.