title: No apparent transmission of transgenic α-synuclein into nigrostriatal dopaminergic neurons in multiple mouse models.
abstract: BACKGROUND
  α-synuclein (α-syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson's disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of α-syn to propagate between or across neighboring neurons and supposedly "infect" them with a prion-like mechanism. However, much of this research has used stereotaxic injections of heterologous α-syn fibrils to induce the spreading of inclusions in the rodent brains. Whether α-syn is able to transmit from the host cells to their neighboring cells in vivo is unclear.
  
  
  METHODS
  Using immunestaining, we examined the potential propagation of α-syn into nigrostriatal dopaminergic (DA) neurons in three lines of transgenic mice that overexpress human wild-type α-syn (hα-syn) in different neuron populations.
  
  
  RESULTS
  After testing for three different routes by which hα-syn propagation might occur, we were unable to find any evidence that hα-syn behaved like a prion and could be transmitted overtime into the DA neurons initially lack of hα-syn expression.
  
  
  CONCLUSIONS
  In transgenic mice hα-syn does not have the ability to propagate at pathologically significant levels between or across neurons. It must be noted that these observations do not disprove the studies that show its prion-like qualities, but rather that propagation is not detectable in transgenic models that do not use any injections of heterologous proteins or viral vectors to induce a spreading state.
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA ; Present addresses: Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA.
authors.forename: Namratha
authors.initials: N
authors.lastname: Sastry
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA ; Present addresses: Swarthmore College, Swarthmore, PA 19081 USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Unit on Synapse Development Plasticity, Clinical Brain Disorder Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA ; Present addresses: Centennial High School, Elicott City, MD 21042 USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cai
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA ; Present addresses: George Washington University, Washington, DC 20052 USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Contractor
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgobio
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Chengsong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD 20892-3707 USA.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Cai
keywords: Dopaminergic neurons; Parkinson’s disease; Propagation; Transgenic mice; α-synuclein