MicroRNAs as promising peripheral sensors of prefrontal cortex developmental trajectory and psychiatric risk

Morgunova, Alice; Flores, Cecilia

doi:10.1038/s41386-021-01113-3

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…This damage results in the death of neurons, reducing the size and function of the prefrontal cortex ( 10 ). MicroRNAs (miRNAs) in the prefrontal cortex play a regulatory role in the expression of genes associated with generalized anxiety disorder ( 11 ), influencing the balance and signaling of neurotransmitters like gamma-aminobutyric acid or glutamate, ultimately affecting mood and behavior ( 12 ). Notably, miR-323a-3p has been shown to play a significant role in the regulation of severe depression ( 13 ), while miR-144-5p levels have been associated with depression, anxiety, or stress-related phenotypes ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice

Chen,

Li,

Tong

et al. 2024

Front. Psychiatry

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BackgroundThe gut-brain axis and gut microbiota have emerged as key players in emotional disorders. Recent studies suggest that alterations in gut microbiota may impact psychiatric symptoms through brain miRNA along the gut-brain axis. However, direct evidence linking gut microbiota to the pathophysiology of generalized anxiety disorder (GAD) via brain miRNA is limited. In this study, we explored the effects of fecal microbiota transplantation (FMT) from GAD donors on gut microbiota and prefrontal cortex miRNA in recipient mice, aiming to understand the relationship between these two factors.MethodsAnxiety scores and gut microbiota composition were assessed in GAD patients, and their fecal samples were utilized for FMT in C57BL/6J mice. Anxiety-like behavior in mice was evaluated using open field and elevated plus maze tests. High-throughput sequencing of gut microbiota 16S rRNA and prefrontal cortex miRNA was performed.ResultsThe fecal microbiota of GAD patients exhibited a distinct microbial structure compared to the healthy group, characterized by a significant decrease in Verrucomicrobia and Akkermansia, and a significant increase in Actinobacteria and Bacteroides. Subsequent FMT from GAD patients to mice induced anxiety-like behavior in recipients. Detailed analysis of gut microbiota composition revealed lower abundances of Verrucomicrobia, Akkermansia, Bifidobacterium, and Butyricimonas, and higher abundances of Deferribacteres, Allobaculum, Bacteroides, and Clostridium in mice that received FMT from GAD patients. MiRNA analysis identified five key miRNAs affecting GAD pathogenesis, including mmu-miR-10a-5p, mmu-miR-1224-5p, mmu-miR-218-5p, mmu-miR-10b-5p, and mmu-miR-488-3p. Notably, mmu-miR-488-3p showed a strong negative correlation with Verrucomicrobia and Akkermansia.ConclusionThis study demonstrates that anxiety-like behavior induced by human FMT can be transmitted through gut microbiota and is associated with miRNA expression in the prefrontal cortex. It is inferred that the reduction of Akkermansia caused by FMT from GAD patients leads to the upregulation of mmu-miR-488-3p expression, resulting in the downregulation of its downstream target gene Creb1 and interference with its related signaling pathway. These findings highlight the gut microbiota’s crucial role in the GAD pathophysiology.

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Section: Introductionmentioning

confidence: 99%

Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice

Chen,

Li,

Tong

et al. 2024

Front. Psychiatry

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Preparation and processing of dried blood spots for microRNA sequencing

Morgunova,

Ibrahim,

Chen

et al. 2023

Biology Methods and Protocols

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Dried blood spots (DBS) are biological samples commonly collected from newborns and in geographic areas distanced from laboratory settings for the purposes of disease testing and identification. MicroRNAs – small non-coding RNAs that regulate gene activity at the post-transcriptional level – are emerging as critical markers and mediators of disease, including cancer, infectious diseases and mental disorders. This protocol describes optimized procedural steps for utilizing DBS as a reliable source of biological material for obtaining peripheral microRNA expression profiles. We outline key practices, such as the method of DBS rehydration that maximizes RNA extraction yield, and the use of degenerate oligonucleotide adapters to mitigate ligase-dependent biases that are associated with small RNA sequencing. The standardization of microRNA readout from DBS offers numerous benefits: cost-effectiveness in sample collection and processing, enhanced reliability and consistency of microRNA profiling, and minimal invasiveness that facilitates repeated testing and retention of participants. The use of DBS-based microRNA sequencing is a promising method to investigate disease mechanisms and to advance personalized medicine.

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MicroRNAs as promising peripheral sensors of prefrontal cortex developmental trajectory and psychiatric risk

Cited by 2 publications

References 6 publications

Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice

Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice

Preparation and processing of dried blood spots for microRNA sequencing

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