Your browser doesn't support javascript.
loading
Human tripartite cortical network model for temporal assessment of alpha-synuclein aggregation and propagation in Parkinson's Disease.
Kapucu, Fikret Emre; Tujula, Iisa; Kulta, Oskari; Sukki, Lassi; Ryynänen, Tomi; Gram, Hjalte; Vuolanto, Valtteri; Vinogradov, Andrey; Kreutzer, Joose; Jensen, Poul Henning; Kallio, Pasi; Narkilahti, Susanna.
Afiliación
  • Kapucu FE; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. emre.kapucu@tuni.fi.
  • Tujula I; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Kulta O; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Sukki L; Micro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Ryynänen T; Micro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Gram H; Danish Research Institute of Translational Neuroscience - DANDRITE and Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Vuolanto V; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Vinogradov A; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Kreutzer J; Micro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Jensen PH; Danish Research Institute of Translational Neuroscience - DANDRITE and Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Kallio P; Micro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Narkilahti S; Neuro Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
NPJ Parkinsons Dis ; 10(1): 138, 2024 Jul 28.
Article en En | MEDLINE | ID: mdl-39069518
ABSTRACT
Previous studies have shown that aggregated alpha-synuclein (α-s) protein, a key pathological marker of Parkinson's disease (PD), can propagate between cells, thus participating in disease progression. This prion-like propagation has been widely studied using in vivo and in vitro models, including rodent and human cell cultures. In this study, our focus was on temporal assessment of functional changes during α-s aggregation and propagation in human induced pluripotent stem cell (hiPSC)-derived neuronal cultures and in engineered networks. Here, we report an engineered circular tripartite human neuronal network model in a microfluidic chip integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We observed progressive aggregation of α-s in conventional neuronal cultures and in the exposed (proximal) compartments of circular tripartite networks following exposure to preformed α-s fibrils (PFF). Furthermore, aggregated forms propagated to distal compartments of the circular tripartite networks through axonal transport. We observed impacts of α-s aggregation on both the structure and function of neuronal cells, such as in presynaptic proteins, mitochondrial motility, calcium oscillations and neuronal activity. The model enabled an assessment of the early, middle, and late phases of α-s aggregation and its propagation during a 13-day follow-up period. While our temporal analysis suggested a complex interplay of structural and functional changes during the in vitro propagation of α-s aggregates, further investigation is required to elucidate the underlying mechanisms. Taken together, this study demonstrates the technical potential of our introduced model for conducting in-depth analyses for revealing such mechanisms.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Parkinsons Dis Año: 2024 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Parkinsons Dis Año: 2024 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos