title: The temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice.
abstract: BACKGROUND
  Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS) under the murine Thy1 (mThy1) promoter, a model known to have a particularly high tg expression associated with impaired olfaction.
  
  
  RESULTS
  Survival of newly generated neurons (NeuN-positive) in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor β (PDGF) promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.
  
  
  CONCLUSIONS
  The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Schreglmann
authors.affiliation: IZKF Junior Research Group III and BMBF Research Group Neuroscience, Interdisciplinary Center for Clinical Research, FAU Erlangen-Nürnberg, Nikolaus-Fiebiger Center for Molecular Medicine, Erlangen, Germany; Department of Neurology, FAU Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Regensburger
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, California, CA, United States of America; Department of Pathology, University of California San Diego, La Jolla, California, CA, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, California, CA, United States of America; Department of Pathology, University of California San Diego, La Jolla, California, CA, United States of America.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Institute of Biochemistry, Emil-Fischer-Zentrum, FAU Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Department of Molecular Neurology, FAU Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.affiliation: IZKF Junior Research Group III and BMBF Research Group Neuroscience, Interdisciplinary Center for Clinical Research, FAU Erlangen-Nürnberg, Nikolaus-Fiebiger Center for Molecular Medicine, Erlangen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D020547:Lateral Ventricles / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics*; D000857:Olfaction Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009830:Olfactory Bulb / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D012903:Smell / Q000235:genetics; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D018800:Thy-1 Antigens; D051844:alpha-Synuclein