title: Hippocampal α-synuclein and interneurons in Parkinson's disease: Data from human and mouse models.
abstract: Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients.
  
  
  
  The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed.
  
  
  
  In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus.
  
  
  
  The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Flores-Cuadrado
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ubeda-Bañon
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saiz-Sanchez
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de la Rosa-Prieto
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Alino
authors.initials: A
authors.lastname: Martinez-Marcos
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000378:metabolism*; D014015:Tissue Banks; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: calcium-binding protein; dementia; hippocampus; nonmotor signs; synucleinopathy