Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms

We have studied the neurotoxicity of amyloid-beta (Aβ) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Aβ1-42 compared to vehicle...

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Main Authors: Desmond T. Walsh, Rosa M. Montero, Laura G. Bresciani, Angela Y.T. Jen, Pascale D. Leclercq, Debbie Saunders, Ahmed N. EL-Amir, Lukemann Gbadamoshi, Stephen M. Gentleman, Ling-Sun Jen
Format: Article
Language:English
Published: Elsevier 2002-06-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996102904857
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author Desmond T. Walsh
Rosa M. Montero
Laura G. Bresciani
Angela Y.T. Jen
Pascale D. Leclercq
Debbie Saunders
Ahmed N. EL-Amir
Lukemann Gbadamoshi
Stephen M. Gentleman
Ling-Sun Jen
author_facet Desmond T. Walsh
Rosa M. Montero
Laura G. Bresciani
Angela Y.T. Jen
Pascale D. Leclercq
Debbie Saunders
Ahmed N. EL-Amir
Lukemann Gbadamoshi
Stephen M. Gentleman
Ling-Sun Jen
author_sort Desmond T. Walsh
collection DOAJ
description We have studied the neurotoxicity of amyloid-beta (Aβ) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Aβ1-42 compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Aβ on retinal neurons and an important role for dysfunction of Müller glia in mediating Aβ neurotoxicity.
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spelling doaj.art-3a8d57f3165b469a9d297e22dcd8aff42022-12-21T18:36:26ZengElsevierNeurobiology of Disease1095-953X2002-06-011012027Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect MechanismsDesmond T. Walsh0Rosa M. Montero1Laura G. Bresciani2Angela Y.T. Jen3Pascale D. Leclercq4Debbie Saunders5Ahmed N. EL-Amir6Lukemann Gbadamoshi7Stephen M. Gentleman8Ling-Sun Jen9Department of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomDepartment of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, W6 8RF, United KingdomWe have studied the neurotoxicity of amyloid-beta (Aβ) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Aβ1-42 compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Aβ on retinal neurons and an important role for dysfunction of Müller glia in mediating Aβ neurotoxicity.http://www.sciencedirect.com/science/article/pii/S0969996102904857amyloid-betaneurotoxicityretinal neuronsMüller cellsglial dysfunctionneurodegeneration
spellingShingle Desmond T. Walsh
Rosa M. Montero
Laura G. Bresciani
Angela Y.T. Jen
Pascale D. Leclercq
Debbie Saunders
Ahmed N. EL-Amir
Lukemann Gbadamoshi
Stephen M. Gentleman
Ling-Sun Jen
Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
Neurobiology of Disease
amyloid-beta
neurotoxicity
retinal neurons
Müller cells
glial dysfunction
neurodegeneration
title Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
title_full Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
title_fullStr Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
title_full_unstemmed Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
title_short Amyloid-Beta Peptide Is Toxic to Neurons In Vivo via Indirect Mechanisms
title_sort amyloid beta peptide is toxic to neurons in vivo via indirect mechanisms
topic amyloid-beta
neurotoxicity
retinal neurons
Müller cells
glial dysfunction
neurodegeneration
url http://www.sciencedirect.com/science/article/pii/S0969996102904857
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