The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae

We have previously reported that vision decline was not associated with amyloidogenesis processing in aging C57BL/6J wild-type (WT) mice and in a mouse model of Alzheimer’s disease, the APP<sub>swe</sub>/PS1ΔE9 transgenic mouse model (APP/PS1). This conclusion was drawn using middle-aged...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sandrine Joly, Léa Rodriguez, Vincent Pernet
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease retina aging electroretinogram photoreceptors Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/8e2a9e0d210e44d0999d02d360bdb43f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8e2a9e0d210e44d0999d02d360bdb43f
record_format	dspace
spelling	oai:doaj.org-article:8e2a9e0d210e44d0999d02d360bdb43f2021-11-11T16:49:23ZThe Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae10.3390/ijms2221113441422-00671661-6596https://doaj.org/article/8e2a9e0d210e44d0999d02d360bdb43f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11344https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067We have previously reported that vision decline was not associated with amyloidogenesis processing in aging C57BL/6J wild-type (WT) mice and in a mouse model of Alzheimer’s disease, the APP<sub>swe</sub>/PS1ΔE9 transgenic mouse model (APP/PS1). This conclusion was drawn using middle-aged (10–13 months old) mice. Here, we hypothesized that compared with hippocampal and cortical neurons, the weak amyloidogenic activity of retinal neurons may result in a detectable release of amyloid β (Aβ) only in aged mice, i.e., between 14 and 24 months of age. The aim of the present study was thus to follow potential activity changes in the amyloidogenic and nonamyloidogenic pathways of young (4 months) and old (20–24 months) WT and APP/PS1 mice. Our results showed that in spite of retinal activity loss reported by electroretinogram (ERG) recordings, the level of amyloid beta precursor protein (APP) and its derivatives did not significantly vary in the eyes of old vs. young mice. Strikingly, the ectopic expression of human APP<sub>swe</sub> in APP/PS1 mice did not allow us to detect Aβ monomers at 23 months. In contrast, Aβ was observed in hippocampal and cortical tissues at this age but not at 4 months of life. In contrast, optic nerve transection-induced retinal ganglion cell injury significantly affected the level of retinal APP and the secretion of soluble APP alpha in the vitreous. Collectively, these results suggest that the amyloidogenic and nonamyloidogenic pathways are not involved in visual function decline in aging mice. In WT and APP/PS1 mice, it is proposed that retinal neurons do not have the capacity to secrete Aβ in contrast with other cortical and hippocampal neurons.Sandrine JolyLéa RodriguezVincent PernetMDPI AGarticleAlzheimer’s diseaseretinaagingelectroretinogramphotoreceptorsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11344, p 11344 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease retina aging electroretinogram photoreceptors Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer’s disease retina aging electroretinogram photoreceptors Biology (General) QH301-705.5 Chemistry QD1-999 Sandrine Joly Léa Rodriguez Vincent Pernet The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
description	We have previously reported that vision decline was not associated with amyloidogenesis processing in aging C57BL/6J wild-type (WT) mice and in a mouse model of Alzheimer’s disease, the APP<sub>swe</sub>/PS1ΔE9 transgenic mouse model (APP/PS1). This conclusion was drawn using middle-aged (10–13 months old) mice. Here, we hypothesized that compared with hippocampal and cortical neurons, the weak amyloidogenic activity of retinal neurons may result in a detectable release of amyloid β (Aβ) only in aged mice, i.e., between 14 and 24 months of age. The aim of the present study was thus to follow potential activity changes in the amyloidogenic and nonamyloidogenic pathways of young (4 months) and old (20–24 months) WT and APP/PS1 mice. Our results showed that in spite of retinal activity loss reported by electroretinogram (ERG) recordings, the level of amyloid beta precursor protein (APP) and its derivatives did not significantly vary in the eyes of old vs. young mice. Strikingly, the ectopic expression of human APP<sub>swe</sub> in APP/PS1 mice did not allow us to detect Aβ monomers at 23 months. In contrast, Aβ was observed in hippocampal and cortical tissues at this age but not at 4 months of life. In contrast, optic nerve transection-induced retinal ganglion cell injury significantly affected the level of retinal APP and the secretion of soluble APP alpha in the vitreous. Collectively, these results suggest that the amyloidogenic and nonamyloidogenic pathways are not involved in visual function decline in aging mice. In WT and APP/PS1 mice, it is proposed that retinal neurons do not have the capacity to secrete Aβ in contrast with other cortical and hippocampal neurons.
format	article
author	Sandrine Joly Léa Rodriguez Vincent Pernet
author_facet	Sandrine Joly Léa Rodriguez Vincent Pernet
author_sort	Sandrine Joly
title	The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
title_short	The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
title_full	The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
title_fullStr	The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
title_full_unstemmed	The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae
title_sort	lack of amyloidogenic activity is persistent in old wt and app<sub>swe</sub>/ps1δe9 mouse retinae
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8e2a9e0d210e44d0999d02d360bdb43f
work_keys_str_mv	AT sandrinejoly thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT learodriguez thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT vincentpernet thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT sandrinejoly lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT learodriguez lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT vincentpernet lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae
_version_	1718432251751956480

The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae

Ejemplares similares