| First Author | Blumenstock S | Year | 2017 |
| Journal | EMBO Mol Med | Volume | 9 |
| Issue | 5 | Pages | 716-731 |
| PubMed ID | 28351932 | Mgi Jnum | J:263591 |
| Mgi Id | MGI:6161937 | Doi | 10.15252/emmm.201607305 |
| Citation | Blumenstock S, et al. (2017) Seeding and transgenic overexpression of alpha-synuclein triggers dendritic spine pathology in the neocortex. EMBO Mol Med 9(5):716-731 |
| abstractText | Although misfolded and aggregated alpha-synuclein (alpha-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 alpha-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 alpha-synuclein. Additionally, intracranial injection of preformed alpha-synuclein fibrils was performed to induce cortical alpha-syn pathology. We find that alpha-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 alpha-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. |
