Dataset Information

Altered expression of histamine signaling genes in autism spectrum disorder.

ABSTRACT: The histaminergic system (HS) has a critical role in cognition, sleep and other behaviors. Although not well studied in autism spectrum disorder (ASD), the HS is implicated in many neurological disorders, some of which share comorbidity with ASD, including Tourette syndrome (TS). Preliminary studies suggest that antagonism of histamine receptors 1-3 reduces symptoms and specific behaviors in ASD patients and relevant animal models. In addition, the HS mediates neuroinflammation, which may be heightened in ASD. Together, this suggests that the HS may also be altered in ASD. Using RNA sequencing (RNA-seq), we investigated genome-wide expression, as well as a focused gene set analysis of key HS genes (HDC, HNMT, HRH1, HRH2, HRH3 and HRH4) in postmortem dorsolateral prefrontal cortex (DLPFC) initially in 13 subjects with ASD and 39 matched controls. At the genome level, eight transcripts were differentially expressed (false discovery rate?<0.05), six of which were small nucleolar RNAs (snoRNAs). There was no significant diagnosis effect on any of the individual HS genes but expression of the gene set of HNMT, HRH1, HRH2 and HRH3 was significantly altered. Curated HS gene sets were also significantly differentially expressed. Differential expression analysis of these gene sets in an independent RNA-seq ASD data set from DLPFC of 47 additional subjects confirmed these findings. Understanding the physiological relevance of an altered HS may suggest new therapeutic options for the treatment of ASD.

SUBMITTER: Wright C

PROVIDER: S-EPMC5534955 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Altered expression of histamine signaling genes in autism spectrum disorder.

Wright C C Shin J H JH Rajpurohit A A Deep-Soboslay A A Collado-Torres L L Brandon N J NJ Hyde T M TM Kleinman J E JE Jaffe A E AE Cross A J AJ Weinberger D R DR

Translational psychiatry 20170509 5

The histaminergic system (HS) has a critical role in cognition, sleep and other behaviors. Although not well studied in autism spectrum disorder (ASD), the HS is implicated in many neurological disorders, some of which share comorbidity with ASD, including Tourette syndrome (TS). Preliminary studies suggest that antagonism of histamine receptors 1-3 reduces symptoms and specific behaviors in ASD patients and relevant animal models. In addition, the HS mediates neuroinflammation, which may be hei ...[more]

PMID: 28485729

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Project description:Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

Dataset Information

Altered expression of histamine signaling genes in autism spectrum disorder.

Publications

Altered expression of histamine signaling genes in autism spectrum disorder.

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