Evidence map›Paper›PMID 24121116›Full record

ArticleNeurobiology of disease2014

Region-specific deficits in dopamine, but not norepinephrine, signaling in a novel A30P α-synuclein BAC transgenic mouse.

Tonya N Taylor, Dawid Potgieter, Sabina Anwar, Steven L Senior, Stephanie Janezic, Sarah Threlfell, Brent Ryan, Laura Parkkinen, Thierry Deltheil, Milena Cioroch and 8 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04266457 (Establishing Alpha-synuclein Real Time - Quaking Induced Conversion), which is not on this map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.5field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04266457 withdrawnnot on this mapstarted 2021, after this paper: background citation

Establishing Alpha-synuclein Real Time - Quaking Induced Conversion (RT-QuIC) Assay as a Diagnostic Technique in Rapid Eye Movement (REM) Sleep Behaviour Disorder (RBD)

TypeobservationalSponsorUniversity of EdinburghRan2021 to 2022Enrolled0ConditionsSleep Disorder Rem Sleep Behavior, Parkinson's Disease, Lewy BodyArmsNo Intervention
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Research models to study lewy body dementia.Molecular neurodegeneration · 2025
    Review
  5. Review
  6. Review
  7. Impaired dopamine release in Parkinson's disease.Brain : a journal of neurology · 2023
    Review
  8. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Analysis of Putative Epigenetic Regulatory Elements in theInternational journal of molecular sciences · 2020
    Review
  16. Animal Model for Prodromal Parkinson's Disease.International journal of molecular sciences · 2020
    Review
  17. Noncanonical Roles of hNeural plasticity · 2020
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Tonya N TaylorOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Dawid PotgieterOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Sabina AnwarOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Steven L SeniorOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Stephanie JanezicOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Sarah ThrelfellOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Brent RyanOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Laura ParkkinenOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Thierry DeltheilOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Milena CiorochOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Achilleas LivieratosDepartment of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK; MRC Functional Genomics Unit, University of Oxford, Oxford, UK.
Peter L OliverDepartment of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK; MRC Functional Genomics Unit, University of Oxford, Oxford, UK.
Katie A JenningsOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Kay E DaviesDepartment of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK; MRC Functional Genomics Unit, University of Oxford, Oxford, UK.
Olaf AnsorgeOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, UK.
David M BannermanOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Experimental Psychology, University of Oxford, Oxford, UK.
Stephanie J CraggOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Richard Wade-MartinsOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK. Electronic address: richard.wade-martins@dpag.ox.ac.uk.
University of Oxford · GBJohn Radcliffe Hospital · GB

Funding

Medical Research Council MC_U137761449Medical Research Council MC_UU_12021/2Medical Research Council MR/J004324/1Parkinson's UK G-0801Parkinson's UK G-0803Parkinson's UK G-1003Parkinson's UK J-0901Wellcome Trust 084655Wellcome Trust 087736Wellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder classically characterized by the death of dopamine (DA) neurons in the substantia nigra pars compacta and by intracellular Lewy bodies composed largely of α-synuclein. Approximately 5-10% of PD patients have a familial form of Parkinsonism, including mutations in α-synuclein. To better understand the cell-type specific role of α-synuclein on DA neurotransmission, and the effects of the disease-associated A30P mutation, we generated and studied a novel transgenic model of PD. We expressed the A30P mutant form of human α-synuclein in a spatially-relevant manner from the 111kb SNCA genomic DNA locus on a bacterial artificial chromosome (BAC) insert on a mouse null (Snca-/-) background. The BAC transgenic mice expressed α-synuclein in tyrosine hydroxylase-positive neurons and expression of either A30P α-synuclein or wildtype α-synuclein restored the sensitivity of DA neurons to MPTP in resistant Snca-/- animals. A30P α-synuclein mice showed no Lewy body-like aggregation, and did not lose catecholamine neurons in substantia nigra or locus coeruleus. However, using cyclic voltammetry at carbon-fiber microelectrodes we identified a deficit in evoked DA release in the caudate putamen, but not in the nucleus accumbens, of SNCA-A30P Snca-/- mice but no changes to release of another catecholamine, norepinephrine (NE), in the NE-rich ventral bed nucleus of stria terminalis. SNCA-A30P Snca-/- mice had no overt behavioral impairments but exhibited a mild increase in wheel-running. In summary, this refined PD mouse model shows that A30P α-synuclein preferentially perturbs the dopaminergic system in the dorsal striatum, reflecting the region-specific change seen in PD.

Indexed as

Age Factorsalpha-SynucleinAnimalsBasal GangliaChromosomes, Artificial, BacterialDisease Models, AnimalDopamineDopaminergic NeuronsFemaleHumansMaleMiceMice, Inbred C57BLMice, TransgenicNorepinephrineSeptal Nucleialpha-SynucleinDopamineNorepinephrineBehaviorDopamineNorepinephrineParkinson's diseaseVoltammetryα-Synuclein

Identifiers

PMID24121116
PMCPMC3898275
OpenAlexW1998805702

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.