ArticlePLoS genetics2019
Increased vulnerability of nigral dopamine neurons after expansion of their axonal arborization size through D2 dopamine receptor conditional knockout.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Deep learning approaches for resolving genomic discrepancies in cancer: a systematic review and clinical perspective.Briefings in bioinformatics · 2025Pooled it
- Nigrostriatal dopaminergic vulnerability in Parkinson's disease: Neuroprotective strategies.Neural regeneration research · 2026Article
- POINTseq: Cell-type-specific barcoding reveals single-cell projection architecture of the mouse dopaminergic system.Neuron · 2026Article
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Cell type-specific barcoding reveals the single-neuron projectional architecture of the mouse midbrain dopaminergic system.bioRxiv : the preprint server for biology · 2026Article
- Mouse model of atypical DAT deficiency syndrome uncovers dopamine dysfunction associated with parkinsonism and ADHD.The Journal of clinical investigation · 2026Article
- The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- Chronic hyperactivation of midbrain dopamine neurons causes preferential dopamine neuron degeneration.eLife · 2025Article
- Inflammatory cytokine upd3 induces axon length-dependent synapse removal by glia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Autonomic dysfunction in neurodegenerative disease.Nature reviews. Neuroscience · 2025Review
- Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood.Nutritional neuroscience · 2025Article
- The regulation of NFKB1 on CD200R1 expression and their potential roles in Parkinson's disease.Journal of neuroinflammation · 2024Article
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases.Nature reviews. Neuroscience · 2024Review
- NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.Molecular neurodegeneration · 2024Article
- Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice.Nature communications · 2023Article
- Article
- Selective neurodegeneration generated by intravenous α-synuclein pre-formed fibril administration is not associated with endogenous α-synuclein levels in the rat brain.Brain pathology (Zurich, Switzerland) · 2023Article
- Genetic Evidence for Endolysosomal Dysfunction in Parkinson's Disease: A Critical Overview.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Rare genetic mutations in genes such as Parkin, Pink1, DJ-1, α-synuclein, LRRK2 and GBA are found to be responsible for the disease in about 15% of the cases. A key unanswered question in PD pathophysiology is why would these mutations, impacting basic cellular processes such as mitochondrial function and neurotransmission, lead to selective degeneration of SNc DA neurons? We previously showed in vitro that SNc DA neurons have an extremely high rate of mitochondrial oxidative phosphorylation and ATP production, characteristics that appear to be the result of their highly complex axonal arborization. To test the hypothesis in vivo that axon arborization size is a key determinant of vulnerability, we selectively labeled SNc or VTA DA neurons using floxed YFP viral injections in DAT-cre mice and showed that SNc DA neurons have a much more arborized axon than those of the VTA. To further enhance this difference, which may represent a limiting factor in the basal vulnerability of these neurons, we selectively deleted in mice the DA D2 receptor (D2-cKO), a key negative regulator of the axonal arbour of DA neurons. In these mice, SNc DA neurons have a 2-fold larger axonal arborization, release less DA and are more vulnerable to a 6-OHDA lesion, but not to α-synuclein overexpression when compared to control SNc DA neurons. This work adds to the accumulating evidence that the axonal arborization size of SNc DA neurons plays a key role in their vulnerability in the context of PD.
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