Integrated Profiling Identifies Long-Term Molecular Consequences of Prenatal Dexamethasone Treatment in the Rat Brain—Potential Triggers of Depressive Phenotype and Cognitive Impairment

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Prenatal excess of glucocorticoids (GCs) is considered to be one the highly impacting factors contributing depression development. Although GCs are crucial for normal fetal development and their administration (mainly dexamethasone, DEX) a life-saving procedure those at risk preterm delivery, exposure levels during pregnancy can yield detrimental consequences. Therefore, we aimed systematically investigate brain molecular alterations triggered by prenatal DEX administration. We used rat model based on performed integrative multi-level methylomic, transcriptomic, proteomic analyses adult rats' brains (i.e., frontal cortex (FCx) hippocampus (Hp)) identify outcomes action. Each investigated was significantly affected in long-term manner. Particularly, found 200 CpG islands differentially methylated FCx Hp prenatally DEX-treated rats. Global transcriptomic analysis uncovered differential expression transcripts mostly (271) 1 Hp, while study identified 146 expressed proteins 123 Hp. Among enriched networks, altered pathways involved synaptic plasticity cAMP, calcium, Wnt signaling or tight junctions adhesion molecules), which may contribute cognitive impairment, observed animals. Moreover, FCx, period downregulates ribosome protein genes associated both with large small ribosomal subunit assembly lead global decrease translation synthesis processes and, indirectly, neurotransmission process.

Language: Английский

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Circulating blood circular RNA in Parkinson’s Disease; from involvement in pathology to diagnostic tools in at-risk individuals

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 18, 2024

To identify circRNAs associated with Parkinson's disease (PD) we leveraged two of the largest publicly available studies longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing last visit each participant (N = 1848), analysis that included 1166 participants at least time points. identified 192 differentially expressed circRNAs, effects were sustained during disease, in mutation carriers, diverse ancestry. The to distinguish between PD healthy ROC AUC 0.797. Further, 71 sufficient genetic (AUC71 0.954) and, at-risk 0.929) controls, supporting have potential aid diagnosis PD. Finally, five highly correlated symptom severity. Overall, demonstrated play an important role can be clinically relevant improve diagnostic monitoring.

Language: Английский

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Bioinformatics analysis and machine learning identification of ferroptosis-related biomarkers in epilepsy

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 11, 2023

Abstract Background Epilepsy is one of the common nervous system diseases, and early diagnosis has an important impact on prognosis. Ferroptosis plays role in pathogenesis epilepsy. Using bioinformatics analysis machine learning, we aimed to identify hub genes associated with ferroptosis provide therapeutic targets for Methods Through datasets GSE49030 GSE88992, differentially expressed genes(DEGs) related epilepsy were identified. Functional enrichment ferroptosis-related DEGs was performed, a protein interaction network used top 30 node genes. LASSO, SVM-RFE, random forest learning algorithms employed screen We analyzed infiltration immune cells control group correlation between cells. Finally, value evaluated training set (GSE49030 GSE88992) validation (GSE16969). Results GSE88992 obtained total 1550 DEGs, including 55 DEGs. Enrichment showed that ferroptosis, oxidative stress, inflammatory signaling pathways enriched. Jun Wwtr1 screened as Immunological 9 kinds group. Two mainly NK cell activation. up-regulated epilepsy, AUROC 0.978 0.973 respectively, verified dataset DSE16969. Conclusion Our results suggest are potential biomarkers can influence both onset progression These more evidence

Language: Английский

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Clinical Significance of MicroRNA-330-3p in Plasma Level for Acute Cerebral Infarction

Cerebrovascular Diseases, Journal Year: 2023, Volume and Issue: 53(4), P. 411 - 419

Published: Sept. 29, 2023

<b><i>Introduction:</i></b> The present study was to investigate the clinical role of miR-330-3p in acute cerebral infarction (ACI), including its diagnostic and prognostic potential. Preliminary exploration target genes archived by bioinformatics analysis. <b><i>Methods:</i></b> plasma patients with ACI controls were quantified real-time quantitative PCR. 1-month prognosis evaluated Glasgow Outcome Scale (GOS). correlation between levels GOS scores tested Pearson receiver operating characteristic (ROC) curves established based on expression level different groups. miR-330-3p-targeting analyzed using Venn diagram, protein-protein interaction network, Gene Ontology enrichment <b><i>Results:</i></b> significantly increased compared that healthy controls, ROC curve revealed value for ACI. poor those good prognosis. negatively correlated score, suggesting potential predict One-year survival analysis surviving had lower than deceased. proven death associated synapse-related terms. <b><i>Conclusion:</i></b> upregulated ACI, making it a promising marker could facilitate synaptic plasticity following infarction.

Language: Английский

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