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Jan 04, 2025;15 (1): 749.

Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.

Isabel Bar��n-Mendoza, Luis A M��rquez, Aliesha Gonz��lez Arenas, Jessica Guzm��n-Condado, Vladimir A Mart��nez-Rojas, Johaly Anguiano-Buenfil, Montserrat Mej��a-Hern��ndez, Jorge Luis Almaz��n, Leonor P��rez-Mart��nez, Gustavo Pedraza-Alva, Emilio J Galv��n, Ang��lica Zepeda
Author Information
  1. Isabel Bar��n-Mendoza: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, 04510, Mexico City, Mexico.
  2. Luis A M��rquez: Departamento de Farmacobiolog��a, CINVESTAV Unidad Sur CdMx, Mexico City, Mexico.
  3. Aliesha Gonz��lez Arenas: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, 04510, Mexico City, Mexico.
  4. Jessica Guzm��n-Condado: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, 04510, Mexico City, Mexico.
  5. Vladimir A Mart��nez-Rojas: Departamento de Farmacobiolog��a, CINVESTAV Unidad Sur CdMx, Mexico City, Mexico.
  6. Johaly Anguiano-Buenfil: Departamento de Farmacobiolog��a, CINVESTAV Unidad Sur CdMx, Mexico City, Mexico.
  7. Montserrat Mej��a-Hern��ndez: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, 04510, Mexico City, Mexico.
  8. Jorge Luis Almaz��n: Laboratorio de Neuroinmunobiolog��a, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog��a UNAM, Cuernavaca, Morelos, 62210, Mexico City, Mexico.
  9. Leonor P��rez-Mart��nez: Laboratorio de Neuroinmunobiolog��a, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog��a UNAM, Cuernavaca, Morelos, 62210, Mexico City, Mexico.
  10. Gustavo Pedraza-Alva: Laboratorio de Neuroinmunobiolog��a, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog��a UNAM, Cuernavaca, Morelos, 62210, Mexico City, Mexico.
  11. Emilio J Galv��n: Departamento de Farmacobiolog��a, CINVESTAV Unidad Sur CdMx, Mexico City, Mexico. ejgalvan@cinvestav.mx.
  12. Ang��lica Zepeda: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, 04510, Mexico City, Mexico. azepeda@iibiomedicas.unam.mx.
PMID: 39755808 DOI: 10.1038/s41598-024-84521-x

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 Nrx1�� 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.

Keywords

Contextual fear memory Hiperactivity Hippocampus Long term potentiation Neurodevelopmental disorders Neurophysiology Spatial memory

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