Discovery and validation of CREB1 as a transcription target of icaritin: Implications for the treatment of depressive-like behavior

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111264 - 111264

Published: Feb. 1, 2025

Depression is a prevalent neuropsychiatric disorder characterized by persistent sadness and lack of interest, significantly impacting the quality life. Icaritin, bioactive compound from Herba Epimedii, which has antidepressant-like effects. However, potential target icaritin in brain, especially concerning transcription factors, not well understood. In this study, we demonstrated that ameliorated depressive-like behaviors chronic corticosterone (CORT)-induced mouse model. This study aimed to investigate role modulating activity cAMP-response element binding protein 1 (CREB1), crucial factor implicated neuronal function mood regulation. Through combination virtual screening molecular docking, identified CREB1 as intersections databases, leading selection 43 candidate compounds, among exhibited favorable docking score previously reported antidepressant Biolayer interferometry (BLI) analysis confirmed direct CREB1, with dissociation constant (KD) 7.02E-06 M. Further mutational revealed residues Q65 Q229 were essential for icaritin. Additionally, Quantitative Real-Time PCR (qRT-PCR) treatment upregulated mRNA levels genes hippocampus cortex. Bioinformatics indicated interacts several neuroprotective pathways, reinforcing its significance depression. conclusion, our findings suggest may represent promising therapeutic depression enhancing CREB1-mediated neuroprotection, warranting further investigation into clinical applications underlying mechanisms.

Language: Английский

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Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 4, 2025

Abstract Background Huntington's disease (HD) could cause progressive motor deficits, psychiatric symptoms, and cognitive impairment. With the increasing use of pharmacotherapies theoretically target neurotransmitters, incidence HD is still not decreasing. However, molecular pathogenesis have been illuminate. It momentous to further examine HD. Methods The next generation sequencing dataset GSE105041 was downloaded from Gene Expression Omnibus (GEO) database. Using DESeq2 in R bioconductor package screen differentially expressed genes (DEGs) between samples normal control samples. ontology (GO) term REACTOME pathway enrichment were performed on DEGs. Meanwhile, using Integrated Interactions Database (IID) database Cytoscape software construct protein–protein interaction (PPI) network module analysis, identify hub with highest value node degree, betweenness, stress closeness scores. miRNA-hub gene regulatory TF-hub constructed analyzed. Receiver operating characteristic curves analysis for diagnostic genes. Results We identified 958 DEGs, consisting 479 up regulated DEGs down GO terms analyses by g:Profiler online results revealed that mainly enriched multicellular organismal process, developmental signaling GPCR MHC class II antigen presentation. Network Analyzer plugin PPI network, LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L COMT selected as Hsa-mir-1292-5p, hsa-mir-4521, ESRRB SREBF1 are potential biomarkers predicted be associated Conclusion This study investigated key pathways interactions its complications, which might help reveal correlation complications. current investigation captured prediction, follow-up biological experiments enforced validation.

Language: Английский

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Pleiotropic Effects of Grm7/GRM7 in Shaping Neurodevelopmental Pathways and the Neural Substrate of Complex Behaviors and Disorders

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 392 - 392

Published: March 8, 2025

Natural gene variants of metabotropic glutamate receptor subtype 7 (Grm7), coding for mGluR7, affect individuals’ alcohol-drinking preference. Psychopharmacological investigations have suggested that mGluR7 is also involved in responses to cocaine, morphine, and nicotine exposures. We review the pleiotropic effects Grm7 principle recombinant quantitative trait locus introgression (RQI), which led discovery first mammalian accounting Grm7/GRM7 can play important roles ontogenesis, brain development, predisposition addiction. It other behavioral phenotypes, including emotion, stress, motivated cognition, defensive behavior, pain-related symptoms. This identified pleiotropy modulation neurobehavioral processes by variations Grm7/GRM7. Patterns genes form oligogenic architectures whosecombined additive interaction significantly predispose individuals expressions disorders. Identifying characterizing are necessary understanding complex traits. requires tasks, such as discovering identifying novel genetic elements architecture, unsuitable AI but require classical experimental genetics.

Language: Английский

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Effects of Glutamate on Growth Performance, Gut Digestion and Antioxidant Capacity in Juvenile Little Yellow Croaker

Fishes, Journal Year: 2025, Volume and Issue: 10(4), P. 188 - 188

Published: April 21, 2025

This study is to explore the alleviating effects of glutamate on intestinal damage in cultured little yellow croaker. A total 900 juvenile fish at a weight 30.68 ± 0.12 g were randomly separated into six groups with three replicates each, and fed basic diet (protein 44.42% lipid 12.48%) additional 0.00%, 0.40%, 0.80%, 1.2%, 1.60%, 2.00%. Each replica group consisted 50 breeding barrel (radius 1.0 m, height 1.5 m), experiment lasted for 54 days. The results showed that supplementation 0.4–1.2% significantly improved survival rate, which increased from 75.56% 91.11%, reduced feed conversion rate 1.75 1.57, protein efficiency ratio 1.55 1.85 (p < 0.05). In intestines, addition 0.40–1.2% muscle thickness villus 0.05), as well activities pepsin, trypsin, α-amylase, lipase Enzyme activity analysis indicated enhanced serum Total Superoxide Dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx) antioxidant enzymes Transcriptome 1.2% 0% revealed differentially expressed genes enriched synthesis, nutrient absorption metabolism, viral interaction cytokine receptor pathways. qPCR experiments verified up-regulated expression antioxidant-related genes, including synthetase Nrf2. conclusion, can enhance growth performance, increase digestive capacity, activate synthesis alleviate damage, maintain health.

Language: Английский

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Association Between Single Nucleotide Polymorphisms Within lncRNA NONHSAT102891 and Depression Susceptibility in a Chinese Population

Neuropsychiatric Disease and Treatment, Journal Year: 2023, Volume and Issue: Volume 19, P. 293 - 302

Published: Feb. 1, 2023

Background: Depression is among the most common psychiatric disorders, and a leading cause of global disease burden. Its pathophysiological mechanism unclear, which limits development therapeutic strategies. Long non-coding RNA (lncRNA) single nucleotide polymorphisms (SNPS) may be related. In this study, we aimed to determine effects rs2242385, rs155979, rs3762983, rs3762984 in lncRNA NONHSAT102891 on depression susceptibility Chinese population. Methods: We conducted case-control study cohort 480 patients with 329 healthy controls, performed genotyping by gene sequencing ii. Results: The rs155979 GC genotype was significantly associated increased risk compared controls. Stratified analysis showed 2.08-fold suicide or GG genotype. were not depression. Haploid linkage disequilibrium between rs3762984, CCG haplotype reduced Limitations: sample relatively small, restricted from central southern China. Further, only peripheral blood used for DNA extraction. Conclusion: polymorphism occurrence However, further studies are needed verify reliability our results large populations different ethnic groups. Keywords: depression, SNP, LncRNA

Language: Английский

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Association between Mir-17-92 gene promoter polymorphisms and depression in a Chinese population

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 6, 2024

Abstract Background Depression is a common chronic debilitating disease with heavy social burden. single nucleotide polymorphisms (SNPs) can affect the function of microRNAs (miRNAs), which in turn associated neurological diseases. However, association between SNPs located promoter region miR-17-92 and risk depression remains unclear. Therefore, we investigated rs982873, rs9588884 rs1813389 incidence Chinese population. Methods used GWAS (Genome-wide study) NCBI (National Center for Biotechnology Information) to screen three cluster binding sites. A case-control study (including 555 cases 541 controls) was conducted investigate relationship different regions China. The gene sequencing ii genotype collected blood samples. Results following genotypes were significantly reduced depression: rs982873 TC (TC vs. TT: OR = 0.72, 95% CI, 0.54–0.96, P 0.024; TC/CC 0.74, Cl, 0.56–0.96, 0.025); CG (CG CC: 0.55–0.98, 0.033; CG/GG 0.75, 0.57–0.98, 0.036); AG (AG AA: 0.57-1.00, 0.049; AG/GG 0.76, 0.59-1.00, 0.047). Stratified analysis showed that there no significant correlation SNPS variables such as family history suicidal tendency ( > 0.05). Conclusions our findings suggest rs9588884, may be protective factors depression.

Language: Английский

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Association between miR-17-92 gene promoter polymorphisms and depression in a Chinese population

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

Published: Oct. 17, 2023

Background Depression is a common chronic debilitating disease with heavy social burden. single nucleotide polymorphisms (SNPs) can affect the function of microRNAs (miRNAs), which in turn associated neurological diseases. However, association between SNPs located promoter region miR-17-92 and risk depression remains unclear. Therefore, we investigated rs982873, rs9588884 rs1813389 incidence Chinese population. Methods used GWAS (Genome-wide study) NCBI (National Center for Biotechnology Information) to screen three cluster binding sites. A case-control study (including 555 cases 541 controls) was conducted investigate relationship different regions China. The gene sequencing ii genotype collected blood samples. Results following genotypes were significantly reduced depression: rs982873 TC (TC vs TT: OR = 0.72, 95% CI, 0.54–0.96, P 0.024; TC/CC 0.74, Cl, 0.56–0.96, 0.025); CG (CG CC: 0.55–0.98, 0.033; CG/GG 0.75, 0.57–0.98, 0.036); AG (AG AA: 0.57-1.00, 0.049; AG/GG 0.76, 0.59-1.00, 0.047). Stratified analysis showed that there no significant correlation SNPS variables such as family history suicidal tendency (P > 0.05). Conclusions our findings suggest rs9588884, may be protective factors depression.

Language: Английский

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