Morpho-Functional Changes of Nigral Dopamine Neurons in an α-Synuclein Model of Parkinson's Disease

Autor: Ada Ledonne, Mariangela Massaro Cenere, Emanuela Paldino, Vincenza D'Angelo, Sebastian Luca D'Addario, Nicolas Casadei, Annalisa Nobili, Nicola Berretta, Francesca R. Fusco, Rossella Ventura, Giuseppe Sancesario, Ezia Guatteo, Nicola Biagio Mercuri
Rok vydání: 2022
Předmět:
Zdroj: Movement disorders : official journal of the Movement Disorder SocietyReferences.
ISSN: 1531-8257
Popis: The accumulation of α-synuclein (α-syn) fibrils in intraneuronal inclusions called Lewy bodies and Lewy neurites is a pathological signature of Parkinson's disease (PD). Although several aspects linked to α-syn-dependent pathology (concerning its spreading, aggregation, and activation of inflammatory and neurodegenerative processes) have been under intense investigation, less attention has been devoted to the real impact of α-syn overexpression on structural and functional properties of substantia nigra pars compacta (SNpc) dopamine (DA) neurons, particularly at tardive stages of α-syn buildup, despite this has obvious relevance to comprehending mechanisms beyond PD progression.We aimed to determine the consequences of a prolonged α-syn overexpression on somatodendritic morphology and functions of SNpc DA neurons.We performed immunohistochemistry, stereological DA cell counts, analyses of dendritic arborization, ex vivo patch-clamp recordings, and in vivo DA microdialysis measurements in a 12- to 13-month-old transgenic rat model overexpressing the full-length human α-syn (SncaAged SncaBesides clarifying α-syn-induced pathological landmarks, such evidence reveals compensatory functional mechanisms that nigral DA neurons could adopt during PD progression to counteract neurodegeneration. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Databáze: OpenAIRE