microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder

Perkins, Diana O.; Jeffries, Clark; Jarskog, L. Fredrik; Thomson, J. Michael; Woods, Keith; Newman, Martin A.; Parker, Joel S.; Jin, Jianping; Hammond, Scott M.

doi:10.1186/gb-2007-8-2-r27

Cited by 504 publications

(461 citation statements)

References 55 publications

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“…Among the differentially expressed miRNAs in our study, miR‐212‐5p has been shown to be downregulated in patients with ASD and schizophrenia 9, 36. Reduced expression of miR‐212 and miR‐132 was also observed in human Alzheimer's disease brains 37.…”

Section: Discussionsupporting

confidence: 53%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveMaternal immune activation (MIA) is associated with an increased risk of autism spectrum disorder (ASD) in offspring. Herein, we investigate the altered expression of microRNAs (miRNA), and that of their target genes, in the brains of MIA mouse offspring.MethodsTo generate MIA model mice, pregnant mice were injected with polyriboinosinic:polyribocytidylic acid on embryonic day 12.5. We performed miRNA microarray and mRNA sequencing in order to determine the differential expression of miRNA and mRNA between MIA mice and controls, at 3 weeks of age. We further identified predicted target genes of dysregulated miRNAs, and miRNA‐target interactions, based on the inverse correlation of their expression levels.ResultsMice prenatally subjected to MIA exhibited behavioral abnormalities typical of ASD, such as a lack of preference for social novelty and reduced prepulse inhibition. We found 29 differentially expressed miRNAs (8 upregulated and 21 downregulated) and 758 differentially expressed mRNAs (542 upregulated and 216 downregulated) in MIA offspring compared to controls. Based on expression levels of the predicted target genes, 18 downregulated miRNAs (340 target genes) and three upregulated miRNAs (60 target genes) were found to be significantly enriched among the differentially expressed genes. miRNA and target gene interactions were most significant between mmu‐miR‐466i‐3p and Hfm1 (ATP‐dependent DNA helicase homolog), and between mmu‐miR‐877‐3p and Aqp6 (aquaporin 6).InterpretationOur results provide novel information regarding miRNA expression changes and their putative targets in the early postnatal period of brain development. Further studies will be needed to evaluate potential pathogenic roles of the dysregulated miRNAs.

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Section: Discussionsupporting

confidence: 53%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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“…Therefore the authors hypothesized that the downregulation of miRNAs they observed is due to altered miRNA biogenesis rather than altered transcription of primiRNA. This is in keeping with the speculation that the potential involvement of the DiGeorge critical region gene 8 encoded protein (an RNA-binding protein that assists Drosha in the processing of miRNAs) in schizophrenia is via its regulation of miRNA biogenesis [63].…”

Section: Mirna and Human Diseasessupporting

confidence: 78%

“…By using microarrays spotted with probes against 265 human miRNAs (at a false discovery rate of 5%), the authors found 16 miRNAs to be differentially expressed: 15 showed decreased expression and one showed higher expression in the schizophrenia patients as compared with controls. For miRNAs residing in introns of protein-coding genes, they observed that the ratios of microarray expression levels of miRNA versus mRNA (of the respective host gene) were significantly different for four of the six hosted miRNAs distinguished by schizo-phrenia [63]. Therefore the authors hypothesized that the downregulation of miRNAs they observed is due to altered miRNA biogenesis rather than altered transcription of primiRNA.…”

Section: Mirna and Human Diseasesmentioning

confidence: 95%

“…To search for the candidate miRNAs involved in the etiopathology of this disease, Perkins et al [63] compared the expression of miRNAs from postmortem prefrontal cortex of individuals with schizophrenia with that of unaffected individuals. By using microarrays spotted with probes against 265 human miRNAs (at a false discovery rate of 5%), the authors found 16 miRNAs to be differentially expressed: 15 showed decreased expression and one showed higher expression in the schizophrenia patients as compared with controls.…”

Section: Mirna and Human Diseasesmentioning

confidence: 99%

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MicroRNAs in brain function and disease

Kuß

Chen²

2008

Curr Neurol Neurosci Rep

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MicroRNAs (miRNAs), a class of small, non-protein-coding transcripts about 21 nucleotides long, have recently entered center stage in the study of posttranscriptional gene regulation. They are now thought to be involved in the control of about one third of all protein-coding genes and play a role in the majority of cellular processes that have been studied. We focus on the role of the miRNA pathway in brain development, function, and disease by highlighting recent observations with respect to miRNAmediated gene regulation in neuronal differentiation, synaptic plasticity, and the circadian clock. We also discuss the implications of these findings with respect to the involvement of miRNAs in the etiopathology of brain disorders and pinpoint the emerging therapeutic potential of miRNAs for the treatment of human diseases.

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“…MiR-9 and miR-128a were overexpressed in the brains of Alzheimer's patients and 16 miRNAs were differentially expressed in the brains of schizophrenics. A mutation in the 3' UTR of the SLITRK1 gene that is associated with Tourette's syndrome led to enhanced repression by miR-189 [84][85][86][87]. Several hundreds of miRNAs were identified in human but currently, only a couple of specific targets have been experimentally validated.…”

Section: Mirnas-associated Disease Mechanismsmentioning

confidence: 99%