title: α-Synuclein staging in the amygdala of a Parkinson's disease model: cell types involved.
abstract: Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α-synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co-localisation of these markers with α-synuclein was performed. Triple labeling of calbindin, somatostatin and α-synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α-Synuclein-positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non-significant increase over time from 16 to 30-43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α-Synuclein mostly co-localised with calbindin and a number of these cells also co-expressed somatostatin. These data on α-synucleinopathy staging in the amygdala could help to explain non-motor symptoms as well as to understand the progression of Parkinson's disease in the brain.
authors.affiliation: Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avda Moledores S/N, 13005, Ciudad Real, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Flores-Cuadrado
authors.forename: Isabel
authors.initials: I
authors.lastname: Ubeda-Bañon
authors.forename: Daniel
authors.initials: D
authors.lastname: Saiz-Sanchez
authors.forename: Carlos
authors.initials: C
authors.lastname: de la Rosa-Prieto
authors.forename: Alino
authors.initials: A
authors.lastname: Martinez-Marcos
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000679:Amygdala / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D013004:Somatostatin / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D013004:Somatostatin
keywords: anhedonia; calcium-binding protein; non-motor symptoms; synucleinopathy; transgenic mice