Gene network analysis reveals a role for striatal glutamatergic receptors in dysregulated risk-assessment behavior of autism mouse models

Oded Oron, Dmitriy Getselter, Shahar Shohat, Eli Reuveni, Iva Lukic, Sagiv Shifman, Evan Elliott

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Autism spectrum disorder (ASD) presents a wide, and often varied, behavioral phenotype. Improper assessment of risks has been reported among individuals diagnosed with ASD. Improper assessment of risks may lead to increased accidents and self-injury, also reported among individuals diagnosed with ASD. However, there is little knowledge of the molecular underpinnings of the impaired risk-assessment phenotype. In this study, we have identified impaired risk-assessment activity in multiple male ASD mouse models. By performing network-based analysis of striatal whole transcriptome data from each of these ASD models, we have identified a cluster of glutamate receptor-associated genes that correlate with the risk-assessment phenotype. Furthermore, pharmacological inhibition of striatal glutamatergic receptors was able to mimic the dysregulation in risk-assessment. Therefore, this study has identified a molecular mechanism that may underlie risk-assessment dysregulation in ASD.

Original languageEnglish
Article number257
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
StatePublished - 17 Oct 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Funding

We would like to thank Dr. Milana Morgenstern and the Center for Genomic Regulation at the Barcelona Biomedical Research Park for their help in genomic sequencing and sequencing analysis. The work was funded by Israel Science Foundation, Grant nos. 1072/42 and 898/17.

FundersFunder number
Israel Science Foundation898/17, 1072/42

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