Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy
Abstract 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 d...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-022-01489-3 |
| _version_ | 1797952259140616192 |
|---|---|
| author | L. Arouche-Delaperche S. Cadoni C. Joffrois G. Labernede M. Valet Q. César J. Dégardin S. Girardon C. Gabriel S. Krantic S. Picaud |
| author_facet | L. Arouche-Delaperche S. Cadoni C. Joffrois G. Labernede M. Valet Q. César J. Dégardin S. Girardon C. Gabriel S. Krantic S. Picaud |
| author_sort | L. Arouche-Delaperche |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T22:44:32Z |
| format | Article |
| id | doaj.art-0a7a8d6064dd459fb3e4b09eda8e565c |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-10T22:44:32Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-0a7a8d6064dd459fb3e4b09eda8e565c2023-01-15T12:24:00ZengBMCActa Neuropathologica Communications2051-59602023-01-0111111710.1186/s40478-022-01489-3Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathyL. Arouche-Delaperche0S. Cadoni1C. Joffrois2G. Labernede3M. Valet4Q. César5J. Dégardin6S. Girardon7C. Gabriel8S. Krantic9S. Picaud10INSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéInstitut de Recherches ServierInstitut de Recherches Internationales ServierINSERM UMRS 938, Centre de Recherche Saint Antoine, CRSA, Sorbonne UniversitéINSERM, CNRS, Institut de La Vision, Sorbonne UniversitéAbstract 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.https://doi.org/10.1186/s40478-022-01489-3RetinaPhosphorylated tauAlzheimer’s diseaseP301S mouseSynapsis |
| spellingShingle | L. Arouche-Delaperche S. Cadoni C. Joffrois G. Labernede M. Valet Q. César J. Dégardin S. Girardon C. Gabriel S. Krantic S. Picaud Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy Acta Neuropathologica Communications Retina Phosphorylated tau Alzheimer’s disease P301S mouse Synapsis |
| title | Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy |
| title_full | Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy |
| title_fullStr | Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy |
| title_full_unstemmed | Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy |
| title_short | Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy |
| title_sort | dysfunction of the glutamatergic photoreceptor synapse in the p301s mouse model of tauopathy |
| topic | Retina Phosphorylated tau Alzheimer’s disease P301S mouse Synapsis |
| url | https://doi.org/10.1186/s40478-022-01489-3 |
| work_keys_str_mv | AT larouchedelaperche dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT scadoni dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT cjoffrois dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT glabernede dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT mvalet dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT qcesar dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT jdegardin dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT sgirardon dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT cgabriel dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT skrantic dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy AT spicaud dysfunctionoftheglutamatergicphotoreceptorsynapseinthep301smousemodeloftauopathy |