Revealing subcellular retinal alterations in 5xFAD B6SJLF1/J mice
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Le résumé fourni par la source
The 5xFAD mouse model recapitulates key pathological features of Alzheimer's disease (AD). However, it remains unclear whether JNK activation represents a common pathogenic mechanism driving both retinal and cerebral neurodegeneration. Establishing such a shared pathway would significantly enhance the retina's potential as an accessible window into the central nervous system (CNS) for monitoring AD progression. We analyzed total retinal homogenates and postsynaptic-enriched protein fractions from 2, 4, 6, and 10-month-old 5xFAD B6SJLF1/J mice using Western blotting and immunofluorescence staining. Key markers of JNK signaling (JNK, p-JNK, JNK3, c-Jun, p-c-Jun) and synaptic integrity (PSD95, p-PSD95) were examined. Additionally, we assessed gliosis (GFAP) and amyloid pathology (APP, p-APP) to evaluate retinal AD progression. Finally, we compared retinal layer thickness between 5xFAD and wild-type (WT) mice across these age points. Although Western blotting revealed no significant JNK signaling activation in total retinal homogenates, synaptic dysfunction was evident through increased PSD95 phosphorylation in 5xFAD mice. Immunofluorescence analysis demonstrated elevated JNK3 immunoreactivity and gliosis in transgenic animals compared to controls. Notably, while WT mice exhibited age-related inner nuclear layer (INL) thinning, 5xFAD mice maintained stable INL thickness and showed progressive total retinal thickening. These findings demonstrate fundamental differences in AD pathology between retinal and brain tissues in 5xFAD B6SJLF1/J mice. The weak JNK activation signature observed in retinal tissue, contrasting with robust brain pathology, suggests current limitations in developing retinal biomarkers for AD detection. Furthermore, our results underscore the necessity of both technical refinement and cautious cross-species interpretation when evaluating the retina's potential as a CNS disease monitor.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Revealing subcellular retinal alterations in 5xFAD B6SJLF1/J mice
- Date Crossref
- 01/07/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Mario Negri Institute for Pharmacological Research pays non établi dans la noticeOrganisation à but non lucratif
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Marche Polytechnic University Department of Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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IRCCS Ospedale San Raffaele pays non établi dans la noticeÉtablissement de santé
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Amsterdam University Medical Centers pays non établi dans la noticeÉtablissement de santé
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University of Amsterdam Department of Ophthalmology pays non établi dans la noticeUniversité ou école supérieure
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University of Milan Department of Pharmacological and Biomolecular Sciences pays non établi dans la noticeUniversité ou école supérieure
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Diabetes Research Institute Complications of Diabetes Unit pays non établi dans la noticeStructure de recherche
Mario Negri Institute for Pharmacological Research, Department of Neuroscience — Marche Polytechnic University et IRCCS Ospedale San Raffaele, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.