Alzheimer's Disease-Related Protein Expression in the Retina of Octodon degus

被引:42
作者
Du, Lucia Y. [1 ]
Chang, Lily Y-L. [1 ]
Ardiles, Alvaro O. [3 ]
Tapia-Rojas, Cheril [4 ]
Araya, Joaquin [3 ]
Inestrosa, Nibaldo C. [4 ]
Palacios, Adrian G. [3 ]
Acosta, Monica L. [1 ,2 ]
机构
[1] Univ Auckland, Sch Optometry & Vis Sci, Auckland 1, New Zealand
[2] Univ Auckland, New Zealand Natl Eye Ctr, Auckland 1, New Zealand
[3] Univ Valparaiso, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso, Chile
[4] Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Cell & Mol Biol, Ctr Aging & Regenerat CARE, Santiago, Chile
来源
PLOS ONE | 2015年 / 10卷 / 08期
关键词
AMYLOID PRECURSOR PROTEIN; TRANSGENIC MICE; MOUSE MODEL; COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E; BETA-PEPTIDE; RAT-BRAIN; IN-VIVO; TAU; PATHOLOGY;
D O I
10.1371/journal.pone.0135499
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
New studies show that the retina also undergoes pathological changes during the development of Alzheimer's disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with A beta aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. A beta 4G8 and A beta 6E10 detected A beta peptides in some of the young animals but the expression was higher in the adults. A beta peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected A beta oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that A beta peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye.
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页数:17
相关论文
共 54 条
[1]   Creatine transporter localization in developing and adult retina: importance of creatine to retinal function [J].
Acosta, ML ;
Kalloniatis, M ;
Christie, DL .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2005, 289 (04) :C1015-C1023
[2]  
Alzheimer A, 1995, Clin Anat, V8, P429
[3]  
Ardiles Alvaro O, 2013, Cold Spring Harb Protoc, V2013, P312, DOI 10.1101/pdb.emo071357
[4]   Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease [J].
Ardiles, Alvaro O. ;
Tapia-Rojas, Cheril C. ;
Mandal, Madhuchhanda ;
Alexandre, Frederic ;
Kirkwood, Alfredo ;
Inestrosa, Nibaldo C. ;
Palacios, Adrian G. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (34) :13835-13840
[5]   Human and rodent amyloid-β peptides differentially bind heme: Relevance to the human susceptibility to Alzheimer's disease [J].
Atamna, Hani ;
Frey, William H., II ;
Ko, Novie .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2009, 487 (01) :59-65
[6]   Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease [J].
Beck, JA ;
Poulter, M ;
Campbell, TA ;
Uphill, JB ;
Adamson, G ;
Geddes, JF ;
Revesz, T ;
Davis, MB ;
Wood, NW ;
Collinge, J ;
Tabrizi, SJ .
HUMAN MOLECULAR GENETICS, 2004, 13 (12) :1219-1224
[7]   Amyloid-β and Tau Pathology of Alzheimer's Disease Induced by Diabetes in a RABBIT Animal Model [J].
Bitel, Claudine L. ;
Kasinathan, Chinnaswamy ;
Kaswala, Rajesh H. ;
Klein, William L. ;
Frederikse, Peter H. .
JOURNAL OF ALZHEIMERS DISEASE, 2012, 32 (02) :291-305
[8]   RETINAL GANGLION-CELL DEGENERATION IN ALZHEIMERS-DISEASE [J].
BLANKS, JC ;
HINTON, DR ;
SADUN, AA ;
MILLER, CA .
BRAIN RESEARCH, 1989, 501 (02) :364-372
[9]   Retinal pathology in Alzheimer's disease .1. Ganglion cell loss in foveal/parafoveal retina [J].
Blanks, JC ;
Torigoe, Y ;
Hinton, DR ;
Blanks, RHI .
NEUROBIOLOGY OF AGING, 1996, 17 (03) :377-384
[10]   Retinal pathology in Alzheimer's disease .2. Regional neuron loss and glial changes in GCL [J].
Blanks, JC ;
Schmidt, SY ;
Torigoe, Y ;
Porrello, KV ;
Hinton, DR ;
Blanks, RHI .
NEUROBIOLOGY OF AGING, 1996, 17 (03) :385-395