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Shank2/3 double knockout-based screening of cortical subregions links the retrosplenial area to the loss of social memory in autism spectrum disorders
- Source :
- Molecular psychiatry 27(12), 4994-5006 (2022). doi:10.1038/s41380-022-01756-8
- Publication Year :
- 2022
- Publisher :
- Macmillan, 2022.
-
Abstract
- Members of the Shank protein family are master scaffolds of the postsynaptic architecture and mutations within the SHANK genes are causally associated with autism spectrum disorders (ASDs). We generated a Shank2-Shank3 double knockout mouse that is showing severe autism related core symptoms, as well as a broad spectrum of comorbidities. We exploited this animal model to identify cortical brain areas linked to specific autistic traits by locally deleting Shank2 and Shank3 simultaneously. Our screening of 10 cortical subregions revealed that a Shank2/3 deletion within the retrosplenial area severely impairs social memory, a core symptom of ASD. Notably, DREADD-mediated neuronal activation could rescue the social impairment triggered by Shank2/3 depletion. Data indicate that the retrosplenial area has to be added to the list of defined brain regions that contribute to the spectrum of behavioural alterations seen in ASDs.<br />publishedVersion
- Subjects :
- Molekularbiologie
Autism Spectrum Disorder
Molecular biology
Social Interaction
Shank2 protein, mouse
Nerve Tissue Proteins
Autismus
Cellular and Molecular Neuroscience
Mice
DDC 570 / Life sciences
ddc:570
metabolism [Gyrus Cinguli]
Shank3 protein, mouse
Animals
ddc:610
Molecular Biology
genetics [Nerve Tissue Proteins]
Neurons
FOS: Clinical medicine
Microfilament Proteins
Neurosciences
Autism spectrum disorders
physiology [Neurons]
Psychiatry and Mental health
Mutation
pathology [Gyrus Cinguli]
genetics [Autism Spectrum Disorder]
genetics [Microfilament Proteins]
DDC 610 / Medicine & health
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular psychiatry 27(12), 4994-5006 (2022). doi:10.1038/s41380-022-01756-8
- Accession number :
- edsair.doi.dedup.....8bdd439bd2ea247f1ff0ca2a0e2c6dcb