Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy.

Mice Animals Alzheimer Disease / pathology tau Proteins / metabolism Mice, Transgenic Tauopathies / pathology Synapses / metabolism Disease Models, Animal
Alzheimer’s disease P301S mouse Phosphorylated tau Retina Synapsis

Journal

Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673

Informations de publication

Date de publication:
11 01 2023
Historique:
received: 13 10 2022
accepted: 04 12 2022
entrez: 11 1 2023
pubmed: 12 1 2023
medline: 14 1 2023
Statut: epublish

Résumé

Tauopathies, including Alzheimer's disease, are characterized by retinal ganglion cell loss associated with amyloid and phosphorylated tau deposits. We investigated the functional impact of these histopathological alterations in the murine P301S model of tauopathy. Visual impairments were demonstrated by a decrease in visual acuity already detectable at 6 months, the onset of disease. Visual signals to the cortex and retina were delayed at 6 and 9 months, respectively. Surprisingly, the retinal output signal was delayed at the light onset and advanced at the light offset. This antagonistic effect, due to a dysfunction of the cone photoreceptor synapse, was associated with changes in the expression of the vesicular glutamate transporter and a microglial reaction. This dysfunction of retinal glutamatergic synapses suggests a novel interpretation for visual deficits in tauopathies and it highlights the potential value of the retina for the diagnostic assessment and the evaluation of therapies in Alzheimer's disease and other tauopathies.

Identifiants

DOI: 10.1186/s40478-022-01489-3 PMID: 36631898 PMC: PMC9832799
pubmed: 36631898
doi: 10.1186/s40478-022-01489-3
pii: 10.1186/s40478-022-01489-3
pmc: PMC9832799
doi:

Substances chimiques

tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5

Informations de copyright

© 2023. The Author(s).

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Auteurs

L Arouche-Delaperche (L)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France. Louiza.arouche@inserm.fr.
ORCID: 0000-0002-5480-3429

S Cadoni (S)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

C Joffrois (C)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

G Labernede (G)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

M Valet (M)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

Q César (Q)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

J Dégardin (J)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.

S Girardon (S)

Institut de Recherches Servier, 125 Chemin de Ronde, 78290, Croissy-Sur-Seine, France.

C Gabriel (C)

Institut de Recherches Internationales Servier, 50 Rue Carnot, 92284, Suresnes, France.

S Krantic (S)

INSERM UMRS 938, Centre de Recherche Saint Antoine, CRSA, Sorbonne Université, 184 Rue Faubourg St Antoine, 75012, Paris, France.

S Picaud (S)

INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France. Serge.picaud@inserm.fr.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Eucaryotes › Animaux › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Tauopathies › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › Dysfunction of the glutamatergic photoreceptor...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Dysfunction of the glutamatergic photoreceptor...