Seeding and transgenic overexpression of alpha-synuclein triggers dendritic spine pathology in the neocortex.
EMBO Mol Med
; 9(5): 716-731, 2017 05.
Article
in En
| MEDLINE
| ID: mdl-28351932
ABSTRACT
Although misfolded and aggregated α-synuclein (α-syn) is recognized in the disease progression of synucleinopathies, its role in the impairment of cortical circuitries and synaptic plasticity remains incompletely understood. We investigated how α-synuclein accumulation affects synaptic plasticity in the mouse somatosensory cortex using two distinct approaches. Long-term in vivo imaging of apical dendrites was performed in mice overexpressing wild-type human α-synuclein. Additionally, intracranial injection of preformed α-synuclein fibrils was performed to induce cortical α-syn pathology. We find that α-synuclein overexpressing mice show decreased spine density and abnormalities in spine dynamics in an age-dependent manner. We also provide evidence for the detrimental effects of seeded α-synuclein aggregates on dendritic architecture. We observed spine loss as well as dystrophic deformation of dendritic shafts in layer V pyramidal neurons. Our results provide a link to the pathophysiology underlying dementia associated with synucleinopathies and may enable the evaluation of potential drug candidates on dendritic spine pathology in vivo.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Up-Regulation
/
Neocortex
/
Dendritic Spines
/
Alpha-Synuclein
/
Protein Aggregation, Pathological
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
EMBO Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2017
Document type:
Article
Affiliation country:
Germany