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Differential Expression of Hippocampal Circular RNAs in the BTBR Mouse Model for Autism Spectrum Disorder.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2020 May; Vol. 57 (5), pp. 2301-2313. Date of Electronic Publication: 2020 Feb 04. - Publication Year :
- 2020
-
Abstract
- Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with unknown etiology. Recent experimental evidences suggest the contribution of non-coding RNAs (ncRNAs) in the pathophysiology of ASD. In this work, we aimed to investigate the expression profile of the ncRNA class of circular RNAs (circRNAs) in the hippocampus of the BTBR T + tf/J (BTBR) mouse model and age-matched C57BL/6J (B6) mice. Alongside, we analyzed BTBR hippocampal gene expression profile to evaluate possible correlations between the differential abundance of circular and linear gene products. From RNA sequencing data, we identified circRNAs highly modulated in BTBR mice. Thirteen circRNAs and their corresponding linear isoforms were validated by RT-qPCR analysis. The BTBR-regulated circCdh9 was better characterized in terms of molecular structure and expression, highlighting altered levels not only in the hippocampus, but also in the cerebellum, prefrontal cortex, and amygdala. Finally, gene expression analysis of the BTBR hippocampus pinpointed altered biological and molecular pathways relevant for the ASD phenotype. By comparison of circRNA and gene expression profiles, we identified 6 genes significantly regulated at either circRNA or mRNA gene products, suggesting low overall correlation between circRNA and host gene expression. In conclusion, our results indicate a consistent deregulation of circRNA expression in the hippocampus of BTBR mice. ASD-related circRNAs should be considered in functional studies to identify their contribution to the etiology of the disorder. In addition, as abundant and highly stable molecules, circRNAs represent interesting potential biomarkers for autism.
- Subjects :
- Animals
Autism Spectrum Disorder genetics
Brain Chemistry
Gene Expression Profiling
Gene Ontology
Humans
Male
Mice, Inbred C57BL
Mice, Inbred Strains genetics
Mice, Mutant Strains genetics
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Autism Spectrum Disorder metabolism
Disease Models, Animal
Hippocampus metabolism
Mice, Inbred Strains metabolism
Mice, Mutant Strains metabolism
RNA, Circular biosynthesis
RNA, Messenger biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 57
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 32020500
- Full Text :
- https://doi.org/10.1007/s12035-020-01878-6