title: Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
abstract: BACKGROUND
  Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD.
  
  
  RESULTS
  The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
  
  
  CONCLUSIONS
  The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.
authors.affiliation: Department of Pathology and Environmental Health Sciences, The Geffen School of Medicine and School of Public Health, University of California, Los Angeles, 650 Charles E, Young Dr. S, CHS 71-295, Los Angeles, CA 90095, USA. yofrecabeza@gmail.com
authors.forename: Yofre
authors.initials: Y
authors.lastname: Cabeza-Arvelaiz
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Fleming
authors.forename: Franziska
authors.initials: F
authors.lastname: Richter
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Chesselet
authors.forename: Robert H
authors.initials: RH
authors.lastname: Schiestl
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000166:cytology* / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D046228:Microarray Analysis; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; C497604:SNCA protein, human; D051844:alpha-Synuclein