ArticleAging cell2021
Vesicular glutamate transporter modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Sexual dimorphism of midbrain catecholaminergic metabolism revealed by neuromelanin-sensitive MRI.Molecular psychiatry · 2026Article
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Aging and Peripheral Nerve Injuries: Impaired Repair, Inflammaging Impact, and Regeneration Resistance.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
- Cellular senescence in age-related musculoskeletal diseases: intercellular communication as a driver of disease pathogenesis.Frontiers of medicine · 2025Article
- A rationally designed microbial consortium modulates neurodegeneration in a Drosophila melanogaster model of Parkinson's disease.NPJ biofilms and microbiomes · 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
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.Molecular psychiatry · 2025Article
- Parallel Gene Expression Changes in Ventral Midbrain Dopamine and GABA Neurons during Normal Aging.eNeuro · 2025Article
- Dopamine-Glutamate and Dopamine-GABA Co-release.Advances in neurobiology · 2025Review
- Review
- ChangPu YuJin Tang improves Tourette disorder symptoms by modulating amino acid neurotransmitters in IDPN model rats.Metabolic brain disease · 2024Article
- Dopamine neurons that inform Drosophila olfactory memory have distinct, acute functions driving attraction and aversion.PLoS biology · 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
- Alterations in neurotransmitter co-release in Parkinson's disease.Experimental neurology · 2023Review
- Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
Age is the greatest risk factor for Parkinson's disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. Intriguingly, some DA neurons are more resilient to degeneration than others. Increasing evidence suggests that vesicular glutamate transporter (VGLUT) expression in DA neurons plays a role in this selective vulnerability. We investigated the role of DA neuron VGLUT in sex- and age-related differences in DA neuron vulnerability using the genetically tractable Drosophila model. We found sex differences in age-related DA neurodegeneration and its associated locomotor behavior, where males exhibit significantly greater decreases in both DA neuron number and locomotion during aging compared with females. We discovered that dynamic changes in DA neuron VGLUT expression mediate these age- and sex-related differences, as a potential compensatory mechanism for diminished DA neurotransmission during aging. Importantly, female Drosophila possess higher levels of VGLUT expression in DA neurons compared with males, and this finding is conserved across flies, rodents, and humans. Moreover, we showed that diminishing VGLUT expression in DA neurons eliminates females' greater resilience to DA neuron loss across aging. This offers a new mechanism for sex differences in selective DA neuron vulnerability to age-related DA neurodegeneration. Finally, in mice, we showed that the ability of DA neurons to achieve optimal control over VGLUT expression is essential for DA neuron survival. These findings lay the groundwork for the manipulation of DA neuron VGLUT expression as a novel therapeutic strategy to boost DA neuron resilience to age- and PD-related neurodegeneration.
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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.