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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/21/11344 |
| _version_ | 1797512506656161792 |
|---|---|
| author | Sandrine Joly Léa Rodriguez Vincent Pernet |
| author_facet | Sandrine Joly Léa Rodriguez Vincent Pernet |
| author_sort | Sandrine Joly |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:02:48Z |
| format | Article |
| id | doaj.art-8e2a9e0d210e44d0999d02d360bdb43f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:02:48Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8e2a9e0d210e44d0999d02d360bdb43f2023-11-22T20:50:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211134410.3390/ijms222111344The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse RetinaeSandrine Joly0Léa Rodriguez1Vincent Pernet2Centre de Recherche du CHU de Québec-Université Laval and Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec-Université Laval and Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec-Université Laval and Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec, QC G1V 4G2, CanadaWe 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.https://www.mdpi.com/1422-0067/22/21/11344Alzheimer’s diseaseretinaagingelectroretinogramphotoreceptors |
| spellingShingle | Sandrine Joly Léa Rodriguez Vincent Pernet The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP<sub>swe</sub>/PS1ΔE9 Mouse Retinae International Journal of Molecular Sciences Alzheimer’s disease retina aging electroretinogram photoreceptors |
| title | 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_short | 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 |
| topic | Alzheimer’s disease retina aging electroretinogram photoreceptors |
| url | https://www.mdpi.com/1422-0067/22/21/11344 |
| work_keys_str_mv | AT sandrinejoly thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT learodriguez thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT vincentpernet thelackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT sandrinejoly lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT learodriguez lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae AT vincentpernet lackofamyloidogenicactivityispersistentinoldwtandappsubswesubps1de9mouseretinae |