Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats Following Acute Corticosterone Administration

Corrales, Wladimir A.; Silva, Juan P.; Parra, C.; Olave, Felipe Antonio; Aguayo, Felipe I.; Román-Albasini, Luciano; Aliaga, Esteban; Venegas-Zamora, Leslye; Avalos, Ana M.; Rojas, Paulina S.; Maracaja-Coutinho, Vinícius; Oakley, Robert H.; Cidlowski, John A.; Fiedler, Jenny L.

doi:10.1021/acschemneuro.0c00762

Cited by 8 publications

(3 citation statements)

References 109 publications

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“…Since an integral aspect of our analysis was to compare miRNA results across studies with diverse test systems, it’s important to highlight the complexities of comparing miRNA findings across studies with different patient disease backgrounds or differences between in vivo and in vitro disease models. The type of test system (human, in vivo , or in vitro ), species, sex, genetic background, chemical exposure, disease conditions, and biological matrices could all contribute to diversity in miRNA responses when comparing across studies ( Corrales et al , 2021 ; Harrill et al , 2016 ; Razak et al , 2013 ; Wang et al , 2009 ). We believe that an integrative approach, utilizing both chemically induced and disease model miRNA data is necessary to identify relevant miRNA biomarkers that will be useful for predictive safety in patients.…”

Section: Discussionmentioning

confidence: 99%

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

You

Cohen

Pustovalova

et al. 2022

Toxicological Sciences

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Elucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Here, we evaluated five neurotoxicants (acetaminophen [negative control], bisindolylmaleimide-1, colchicine, doxorubicin, paclitaxel, and rotenone) in human iPSC-derived neurons to profile secreted miRNAs at early and late stages of decline in neuronal cell morphology and viability. Based on evaluation of these morphological (neurite outgrowth parameters) and viability (ATP) changes, two concentrations of each chemical were selected for analysis in a human 754 miRNA panel: a low concentration with no/minimal effect on cell viability but a significant decrease in neurite outgrowth, and a high concentration with a significant decrease in both endpoints. A total of 39 miRNAs demonstrated significant changes (fold-change ≥1.5 or ≤ 0.67, p-value < 0.01) with at least one exposure. Further analyses of targets modulated by these miRNAs revealed 38 key mRNA targets with roles in neurological dysfunctions, and identified TGF-β signaling as a commonly enriched pathway. Of the 39 miRNAs, five miRNAs, three down-regulated (miR-20a, miR-30b, and miR-30d) and two up-regulated (miR-1243 and miR-1305), correlated well with morphological changes induced by multiple neurotoxicants and were notable based on their relationship to various neurodegenerative conditions and/or key pathways, such as TGF-β signaling. These data sets reveal miRNA candidates that warrant further evaluation as potential safety biomarkers of chemical-induced neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

You

Cohen

Pustovalova

et al. 2022

Toxicological Sciences

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“…Accumulating research evidences suggest that excessive induction of CORT levels by stress events causes cellular damage and is strongly implicated in the pathogenesis of depression. 19,20) Other studies also indicate that hippocampal neuronal proliferation and growth play crucial roles in the pathological mechanism of depression, so the damage of neuronal cell survival and development caused by CORT exposure can be an effective way to establish a model of depression. 21,22) PC-12 cell line is a neural cell line derived from rats, which is widely used in the study of nervous system diseases.…”

Section: Discussionmentioning

confidence: 99%

Baicalin Coadministration with Lithium Chloride Enhanced Neurogenesis <i>via</i> GSK3β Pathway in Corticosterone Induced PC-12 Cells

Wang

Cheng

et al. 2022

Biological & Pharmaceutical Bulletin

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Accumulating studies suggest that hippocampal neurogenesis plays a crucial role in the pathological mechanism of depression. As a classic antidepressant, lithium chloride can play an antidepressant role by inhibiting GSK3β and promoting neurogenesis. Correspondingly, baicalin is a compound extracted from natural plants, which shows potential antidepressant effect, however, whether baicalin exerts antidepressant effects by promoting neurogenesis still needs further investigation. In the current study, we established an in vitro depression model through corticosterone induced PC-12 cells, and explored the potential mechanism of baicalin's antidepressant effect by comparing it with lithium chloride alone and the coadministration with lithium chloride. We used CCK-8 assay, EdU staining and cell cycle analysis to evaluate the state of cell survival and cell proliferation. The protein expression levels of neurodevelopmental related factors DCX, BDNF, and the GSK3β pathway-related proteins and mRNA were detected by Western blot and Real-time PCR. The results showed that baicalin could decrease the expression level of GSK3β, while upregulate the expression level of DCX, BDNF, Cyclin D1-CDK4/6, thus promoted cell proliferation and survival in CORT induced PC-12 cells. Moreover, this effect was enhanced when baicalin and lithium chloride were coadministration. Taking the above results together, we conclude that baicalin can promote the proliferation and development of PC-12 cells by regulating GSK3β pathway, so as to reverse the depressivelike pathological changes induced by corticosterone.

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“…The influence of sex on miRNA expression has been increasingly studied in the adult brain [20][21][22][23][24][25][26][27] , but few publications address sex-differential miRNA expression during development. Ziats et al (2014) showed sex differences in miRNA expression in the human brain from before birth to adulthood 28 .…”

Section: Introductionmentioning

confidence: 99%

Sex-biased gene and microRNA expression in the developing mouse brain is associated with neurodevelopmental functions and neurological phenotypes

Szakats

McAtamney

Cross

et al. 2022

Preprint

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Background: Sex differences pose a challenge and an opportunity in biomedical research. Understanding how sex chromosomes and hormones affect disease-causing mechanisms will shed light on the mechanisms underlying predominantly idiopathic sex-biased neurodevelopmental disorders such as ADHD, schizophrenia and autism. Gene expression is a crucial conduit for the influence of sex on developmental processes; therefore, this investigation focused on sex differences in gene expression and regulation of gene expression. Mounting interest in microRNAs (miRNAs), small, non-coding RNAs for their contribution to normal and pathological neurodevelopment prompted us to test how miRNA expression differs between the sexes in the developing brain. Methods: High-throughput sequencing approaches were used to identify transcripts, including miRNAs, showing significantly different expression between male and female brains at day 15.5 of development (E15.5). Results: Robust sex differences were identified for a portion of genes and miRNAs, confirming the influence of biological sex on RNA in this context. Many miRNAs showing the greatest differences between males and females have established roles in neurodevelopment, implying that sex-biased expression could drive sex differences in developmental processes. In addition to highlighting sex differences for individual miRNAs, gene ontology analysis suggests several broad categories in which sex-biased RNAs might be acting to establish sex differences in the embryonic mouse brain. Finally, mining publically available SNP data indicated that some sex-biased miRNAs reside near genomic regions associated with neurodevelopmental disorders. Conclusions: Together, these findings reinforce the importance of cataloguing sex differences in molecular biology research and highlight genes, miRNAs and pathways of interest that may be important for sexual differentiation of the mouse and possibly the human brain.

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Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats Following Acute Corticosterone Administration

Cited by 8 publications

References 109 publications

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons

Baicalin Coadministration with Lithium Chloride Enhanced Neurogenesis <i>via</i> GSK3β Pathway in Corticosterone Induced PC-12 Cells

Sex-biased gene and microRNA expression in the developing mouse brain is associated with neurodevelopmental functions and neurological phenotypes

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