Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism
Abstract Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing and behavior. In most cases, autism is considered idiopathic, involving alterations in numerous genes whose functions are not extensively documented. We evaluat...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-84521-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849725117136896000 |
|---|---|
| author | Isabel Barón-Mendoza Luis A. Márquez Aliesha González-Arenas Jessica Guzmán-Condado Vladimir A. Martínez-Rojas Johaly Anguiano-Buenfil Montserrat Mejía-Hernández Jorge Luis Almazán Leonor Pérez-Martínez Gustavo Pedraza-Alva Emilio J. Galván Angélica Zepeda |
| author_facet | Isabel Barón-Mendoza Luis A. Márquez Aliesha González-Arenas Jessica Guzmán-Condado Vladimir A. Martínez-Rojas Johaly Anguiano-Buenfil Montserrat Mejía-Hernández Jorge Luis Almazán Leonor Pérez-Martínez Gustavo Pedraza-Alva Emilio J. Galván Angélica Zepeda |
| author_sort | Isabel Barón-Mendoza |
| collection | DOAJ |
| description | Abstract Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing and behavior. In most cases, autism is considered idiopathic, involving alterations in numerous genes whose functions are not extensively documented. We evaluated the C58/J mouse strain as an idiopathic model of ASD, emphasizing synaptic transmission as the basis of information processing. Through in silico analysis, we found that the C58/J strain carries single nucleotide polymorphisms (SNPs) compared to the C57BL/6J control strain related to synaptic structure and LTP induction. These SNPs have human orthologs previously associated with ASD. We then assessed chemical potentiation (cLTP) in synaptosomes, the electrophysiological properties of hippocampal CA3 cells, and the induction of LTP in ex-vivo slices. An increased proportion of synaptosomes expressing the GluA1 subunit of AMPA receptor and Nrx1β in the membrane was found in the C57BL/6J control strain, but not in C58/J mice, after cLTP induction. Additionally, several electrophysiological properties of CA3 pyramidal cells and hippocampal communication were altered. Behaviorally, C58/J mice exhibited hyperactivity and subtle memory changes. Our results demonstrate that an idiopathic model of ASD exhibits alterations in hippocampal physiology from the cellular to the circuitry and behavioral levels. |
| format | Article |
| id | doaj-art-69d9af1e67014abfacf69da219d21d12 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-69d9af1e67014abfacf69da219d21d122025-08-20T03:10:32ZengNature PortfolioScientific Reports2045-23222025-01-0115112110.1038/s41598-024-84521-xSingle-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autismIsabel Barón-Mendoza0Luis A. Márquez1Aliesha González-Arenas2Jessica Guzmán-Condado3Vladimir A. Martínez-Rojas4Johaly Anguiano-Buenfil5Montserrat Mejía-Hernández6Jorge Luis Almazán7Leonor Pérez-Martínez8Gustavo Pedraza-Alva9Emilio J. Galván10Angélica Zepeda11Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Farmacobiología, CINVESTAV Unidad Sur CdMxDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoDepartamento de Farmacobiología, CINVESTAV Unidad Sur CdMxDepartamento de Farmacobiología, CINVESTAV Unidad Sur CdMxDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoLaboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología UNAMLaboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología UNAMLaboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología UNAMDepartamento de Farmacobiología, CINVESTAV Unidad Sur CdMxDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoAbstract Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing and behavior. In most cases, autism is considered idiopathic, involving alterations in numerous genes whose functions are not extensively documented. We evaluated the C58/J mouse strain as an idiopathic model of ASD, emphasizing synaptic transmission as the basis of information processing. Through in silico analysis, we found that the C58/J strain carries single nucleotide polymorphisms (SNPs) compared to the C57BL/6J control strain related to synaptic structure and LTP induction. These SNPs have human orthologs previously associated with ASD. We then assessed chemical potentiation (cLTP) in synaptosomes, the electrophysiological properties of hippocampal CA3 cells, and the induction of LTP in ex-vivo slices. An increased proportion of synaptosomes expressing the GluA1 subunit of AMPA receptor and Nrx1β in the membrane was found in the C57BL/6J control strain, but not in C58/J mice, after cLTP induction. Additionally, several electrophysiological properties of CA3 pyramidal cells and hippocampal communication were altered. Behaviorally, C58/J mice exhibited hyperactivity and subtle memory changes. Our results demonstrate that an idiopathic model of ASD exhibits alterations in hippocampal physiology from the cellular to the circuitry and behavioral levels.https://doi.org/10.1038/s41598-024-84521-xNeurodevelopmental disordersHippocampusNeurophysiologyLong term potentiationContextual fear memorySpatial memory |
| spellingShingle | Isabel Barón-Mendoza Luis A. Márquez Aliesha González-Arenas Jessica Guzmán-Condado Vladimir A. Martínez-Rojas Johaly Anguiano-Buenfil Montserrat Mejía-Hernández Jorge Luis Almazán Leonor Pérez-Martínez Gustavo Pedraza-Alva Emilio J. Galván Angélica Zepeda Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism Scientific Reports Neurodevelopmental disorders Hippocampus Neurophysiology Long term potentiation Contextual fear memory Spatial memory |
| title | Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| title_full | Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| title_fullStr | Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| title_full_unstemmed | Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| title_short | Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| title_sort | single nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism |
| topic | Neurodevelopmental disorders Hippocampus Neurophysiology Long term potentiation Contextual fear memory Spatial memory |
| url | https://doi.org/10.1038/s41598-024-84521-x |
| work_keys_str_mv | AT isabelbaronmendoza singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT luisamarquez singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT alieshagonzalezarenas singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT jessicaguzmancondado singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT vladimiramartinezrojas singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT johalyanguianobuenfil singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT montserratmejiahernandez singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT jorgeluisalmazan singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT leonorperezmartinez singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT gustavopedrazaalva singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT emiliojgalvan singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism AT angelicazepeda singlenucleotidepolymorphismanalysisaccuratelypredictsmultipleimpairmentsinhippocampalactivityandmemoryperformanceinamurinemodelofidiopathicautism |