Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson's Disease/Dementia with Lewy Bodies

被引：44

作者：

Price, Diana L. ^{[1
]}

Rockenstein, Edward ^{[2
]}

Mante, Michael ^{[2
]}

Adame, Anthony ^{[2
]}

Overk, Cassia ^{[2
]}

Spencer, Brian ^{[2
]}

Duong-Polk, Karen X. ^{[3
]}

Bonhaus, Douglas ^{[1
]}

Lindsey, James ^{[3
]}

Masliah, Eliezer ^{[2
,4
]}

机构：

[1] Neuropore Therapies Inc, San Diego, CA 92121 USA

[2] Univ Calif La Jolla, Dept Neurosci, San Diego, CA 92093 USA

[3] Univ Calif La Jolla, Dept Ophthalmol, San Diego, CA 92093 USA

[4] Univ Calif La Jolla, Dept Pathol, San Diego, CA 92093 USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; DROSOPHILA MODEL; GAMMA-SYNUCLEIN; TAU; PATHOLOGY; NERVE; NEUROTOXICITY; DEGENERATION; AGGREGATION;

D O I：

10.1038/srep29523

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Abnormal alpha-synuclein (alpha-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated alpha-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused alpha-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged alpha-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the alpha-syn::GFP-positive cells were retinal ganglion cells containing alpha-syn. Accumulation of alpha-syn persisted in the same cells and increased with age. Accumulation of alpha-syn::GFP was reduced by immunization with single chain antibodies against alpha-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-alpha-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of alpha-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting alpha-syn.

引用

页数：10

共 46 条

[1] Submandibular gland needle biopsy for the diagnosis of Parkinson disease [J].