title: Social Cognition Impairments in Mice Overexpressing Alpha-Synuclein Under the Thy1 Promoter, a Model of Pre-manifest Parkinson's Disease.
abstract: BACKGROUND
  Patients with Parkinson's disease (PD) may exhibit deficits in "Theory of Mind", the ability to read others' mental states and react appropriately, a prerequisite for successful social interaction. Alpha-synuclein overexpression is widely distributed in the brain of patients with sporadic PD, suggesting that it may contribute to the non-motor deficits observed in PD patients. Mice over-expressing human wild-type alpha-synuclein under the Thy1 promoter (Thy1-aSyn mice) have synaptic deficits in the frontostriatal pathway, low cortical acetylcholine, and high level of expression of mGluR5 receptors, which have all been implicated in social recognition deficits.
  
  
  OBJECTIVE
  To determine whether Thy1-aSyn mice present alterations in their response to social stimuli.
  
  
  METHODS
  We have submitted Thy1-aSyn mice to tests adapted from autism models.
  
  
  RESULTS
  At 7-8 month of age Thy1-aSyn mice explored their conspecifics significantly less than did wild-type littermates, without differences in exploration of inanimate objects, and pairs of Thy1-aSyn mice were involved in reciprocal interactions for a shorter duration than wild-type mice at this age. These deficits persisted when the test animal was enclosed in a beaker and were not present at 3-4 months of age despite the presence of olfactory deficits at that age, indicating that they were not solely caused by impairment in olfaction.
  
  
  CONCLUSIONS
  Thy1-aSyn mice present progressive deficits in social recognition, supporting an association between alpha-synuclein overexpression and Theory of Mind deficits in PD and providing a useful model for identifying mechanisms and testing novel treatments for these deficits which impact patients and caretakers quality of life.
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Iddo
authors.initials: I
authors.lastname: Magen
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Eileen Ruth
authors.initials: ER
authors.lastname: Torres
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Dinh
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chung
authors.affiliation: Department of Neuroscience, University of California, San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Chesselet
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000378:metabolism / Q000523:psychology*; D011401:Promoter Regions, Genetic; D012919:Social Behavior; D056345:Theory of Mind / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Theory of mind; autistic disorder; mGluR5