Limits...
Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.

Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM - Mol Autism (2015)

Bottom Line: We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC).Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.

ABSTRACT

Background: Autism spectrum disorders (ASDs) likely involve dysregulation of multiple genes related to brain function and development. Abnormalities in individual regulatory small non-coding RNA (sncRNA), including microRNA (miRNA), could have profound effects upon multiple functional pathways. We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC).

Methods: We measured sncRNA expression levels in 34 samples of postmortem brain from STS and PAC to find differentially expressed sncRNA in ASD compared with control cases. For differentially expressed miRNA, we further analyzed their predicted mRNA targets and carried out functional over-representation analysis of KEGG pathways to examine their functional significance and to compare our findings to reported alterations in ASD gene expression.

Results: Two mature miRNAs (miR-4753-5p and miR-1) were differentially expressed in ASD relative to control in STS and four (miR-664-3p, miR-4709-3p, miR-4742-3p, and miR-297) in PAC. In both regions, miRNA were functionally related to various nervous system, cell cycle, and canonical signaling pathways, including PI3K-Akt signaling, previously implicated in ASD. Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.

Conclusions: Alterations in sncRNA may underlie dysregulation of molecular pathways implicated in autism. sncRNA transcriptional abnormalities in ASD were apparent in STS and in PAC, a brain region not directly associated with core behavioral impairments. Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

No MeSH data available.


Related in: MedlinePlus

Relative expression of sncRNA in STS and PAC of ASD and CTRL subjects. Heat maps showing hierarchical clustering of dysregulated small non-coding RNAs on the X axis for ASD and control (CTRL) subjects on the Y axis for the superior temporal sulcus (STS) (upper panel) and the primary auditory cortex (PAC) (lower panel). Note that the ASD and CTRL subjects cluster together in both the PAC and STS. Bright red color indicates a relative twofold increase in expression for the particular sncRNA, and a bright green color indicates a relative twofold decrease in expression across ASD and control subjects (see bar at bottom of lower panel)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4491207&req=5

Fig2: Relative expression of sncRNA in STS and PAC of ASD and CTRL subjects. Heat maps showing hierarchical clustering of dysregulated small non-coding RNAs on the X axis for ASD and control (CTRL) subjects on the Y axis for the superior temporal sulcus (STS) (upper panel) and the primary auditory cortex (PAC) (lower panel). Note that the ASD and CTRL subjects cluster together in both the PAC and STS. Bright red color indicates a relative twofold increase in expression for the particular sncRNA, and a bright green color indicates a relative twofold decrease in expression across ASD and control subjects (see bar at bottom of lower panel)

Mentions: There were no significant differences in the sex or age of ASD compared to control subjects (P > 0.05, Table 1). Table 2 lists the sncRNA that were differentially expressed in ASD compared to controls (P < 0.005 and fold change > /1.2/) in the temporal lobe for the superior temporal sulcus (STS) and for the primary auditory cortex (PAC) (detailed fold change and P values provided in Additional file 1: Tables S1 and S2). When subjected to hierarchical clustering, these sncRNA completely separated ASD from control subjects for both the PAC and STS brain regions (Fig. 2), lending further support that these sncRNA were significantly different in ASD compared to controls in both brain regions.Table 2


Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.

Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM - Mol Autism (2015)

Relative expression of sncRNA in STS and PAC of ASD and CTRL subjects. Heat maps showing hierarchical clustering of dysregulated small non-coding RNAs on the X axis for ASD and control (CTRL) subjects on the Y axis for the superior temporal sulcus (STS) (upper panel) and the primary auditory cortex (PAC) (lower panel). Note that the ASD and CTRL subjects cluster together in both the PAC and STS. Bright red color indicates a relative twofold increase in expression for the particular sncRNA, and a bright green color indicates a relative twofold decrease in expression across ASD and control subjects (see bar at bottom of lower panel)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491207&req=5

Fig2: Relative expression of sncRNA in STS and PAC of ASD and CTRL subjects. Heat maps showing hierarchical clustering of dysregulated small non-coding RNAs on the X axis for ASD and control (CTRL) subjects on the Y axis for the superior temporal sulcus (STS) (upper panel) and the primary auditory cortex (PAC) (lower panel). Note that the ASD and CTRL subjects cluster together in both the PAC and STS. Bright red color indicates a relative twofold increase in expression for the particular sncRNA, and a bright green color indicates a relative twofold decrease in expression across ASD and control subjects (see bar at bottom of lower panel)
Mentions: There were no significant differences in the sex or age of ASD compared to control subjects (P > 0.05, Table 1). Table 2 lists the sncRNA that were differentially expressed in ASD compared to controls (P < 0.005 and fold change > /1.2/) in the temporal lobe for the superior temporal sulcus (STS) and for the primary auditory cortex (PAC) (detailed fold change and P values provided in Additional file 1: Tables S1 and S2). When subjected to hierarchical clustering, these sncRNA completely separated ASD from control subjects for both the PAC and STS brain regions (Fig. 2), lending further support that these sncRNA were significantly different in ASD compared to controls in both brain regions.Table 2

Bottom Line: We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC).Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.

ABSTRACT

Background: Autism spectrum disorders (ASDs) likely involve dysregulation of multiple genes related to brain function and development. Abnormalities in individual regulatory small non-coding RNA (sncRNA), including microRNA (miRNA), could have profound effects upon multiple functional pathways. We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC).

Methods: We measured sncRNA expression levels in 34 samples of postmortem brain from STS and PAC to find differentially expressed sncRNA in ASD compared with control cases. For differentially expressed miRNA, we further analyzed their predicted mRNA targets and carried out functional over-representation analysis of KEGG pathways to examine their functional significance and to compare our findings to reported alterations in ASD gene expression.

Results: Two mature miRNAs (miR-4753-5p and miR-1) were differentially expressed in ASD relative to control in STS and four (miR-664-3p, miR-4709-3p, miR-4742-3p, and miR-297) in PAC. In both regions, miRNA were functionally related to various nervous system, cell cycle, and canonical signaling pathways, including PI3K-Akt signaling, previously implicated in ASD. Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.

Conclusions: Alterations in sncRNA may underlie dysregulation of molecular pathways implicated in autism. sncRNA transcriptional abnormalities in ASD were apparent in STS and in PAC, a brain region not directly associated with core behavioral impairments. Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

No MeSH data available.


Related in: MedlinePlus