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Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression [NovaSeq]

ABSTRACT: Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression [NovaSeq]

PROVIDER: PRJNA1075094 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27929302_1.fastq.gz	Fastqsanger.gz
	SRR27929302_2.fastq.gz	Fastqsanger.gz
	SRR27929303_1.fastq.gz	Fastqsanger.gz
	SRR27929303_2.fastq.gz	Fastqsanger.gz
	SRR27929304_1.fastq.gz	Fastqsanger.gz

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Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression

Project description:Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression

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Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression [NovaSeq]

Project description:Major depressive disorder (MDD) is a leading cause of disability with significant mortality risk. Despite progress in our understanding of the etiology of MDD, the underlying molecular changes in the brain remain poorly understood. Extracellular vesicles (EVs) are lipid-bound particles that can reflect the molecular signatures of the tissue of origin. We aimed to optimize a streamlined EV isolation protocol from post-mortem brain tissue and to determine whether EV RNA cargo, particularly microRNAs (miRNAs) have an MDD-specific profile. EVs were isolated from post-mortem human brain tissue. Quality was assessed using western blots, transmission electron microscopy, and microfluidic resistive pulse sensing. EV RNA was extracted and sequenced on Illumina platforms. Functional follow up was performed in silico. Quality assessment showed an enrichment of EV markers, as well as a size distribution of 30-200 nm in diameter, and no contamination with cellular debris. Small RNA profiling indicated the presence of several RNA biotypes, with miRNAs and transfer RNAs (tRNAs) being the most prominent. Exploring miRNA levels between groups revealed decreased expression of miR-92a-3p and miR-129-5p, which was validated by qPCR and was specific to EVs and not seen in bulk tissue. Finally, in silico functional analyses indicate potential roles for these two miRNAs in neurotransmission and synaptic plasticity. We provide a streamlined isolation protocol that yields EVs of high quality that are suitable for molecular follow up. Our findings warrant future investigations into brain EV miRNA dysregulation in MDD.

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Title: Profiling Small RNA from Brain Extracellular Vesicles in Individuals with Depression

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DNA methylation and inflammation marker profiles associated with a history of depression.

Project description:Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n=100) and individuals without a history of depression (n=100) using the Illumina 450K microarray. Our analysis identified 6 significant (Sidak corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidak corrected P = 1.27 x 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.

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