Chronic stress-induced neuroplasticity in the prefrontal cortex: Structural, functional, and molecular mechanisms from development to aging

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149461 - 149461

Published: Jan. 1, 2025

Language: Английский

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Histone monoaminylation is a novel epigenetic mechanism in psychiatric disorders

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Feb. 18, 2025

Monoamines, basic nitrogenous molecules containing one amine group, include serotonin, adrenaline, noradrenaline, dopamine, and histamine. They are mainly synthesized due to decarboxylation of amino acids or by transamination amination ketones aldehydes (Al-Kachak Maze, 2023). important neurotransmitters in the body, especially central nervous system, but also peripheral enteric system.Protein monoaminylation is covalent bonding biogenic monoamines glutamine residues some proteins a transamidation reaction. It was first described Heinrich Waelsch's group 1950s (Sarkar et al. 1957;Al-Kachak This showed that mono-and polyamines can be included into livers obtained from guinea pigs, mice, rats, rabbits, with help calcium-dependent transglutaminases (TGMs). In mammals nine isozymes have been delineated (Zhuang Khosla, 2019). Human TGM2 multifunctional ubiquitous takes part many cellular processes such as apoptosis, development, differentiation, wound healing, angiogenesis (Kim Park, 2020). cell located cytosol, nucleus, surface, extracellularly (Keillor al., 2015). has functions depending on its localization allosterically stimulated calcium ions deactivated guanosine triphosphate comprises 687 acid four-domain structure molecular weight about 70 kDa TGMs cross-link γ-carboxamide residue ϵ-amino lysine 2020), catalyse target (Jiang 2012;Al-Kachak Since work including fibronectin, fibrinogen, actin, myosin found monoaminylated (Bader, 2019),Modifications histones well-established epigenetic mechanism regulation gene expression transduce environmental signals modulate (Vanzan 2023;Wu Histones undergo dynamic reversible biochemical posttranslational modifications (Kennelly Histone acetylation deacetylation best studied undergo. Others methylation, phosphorylation, sumoylation, ADP-ribosylation, citrullination, proline isomerisation 2023).Histone reduce positive charges histone tails hence binding affinity negatively charged DNA Additionally, form extra sites for like ATP-dependent chromatinremodelling complexes which contain subunits specifically attach specific modifications. These may enhance accessibility neighbouring sequences modifying removing histones. The chromatin-remodelling synergistically act open up promoters regulatory regions, thereby permitting trans-factors, RNA polymerase II, general transcription factors (GTFs) 2023).A relatively new type modification (Figure 1). shown chicken erythrocytes Ballestar colleagues (1996). 2019, Ian Maze's using sophisticated techniques methodologies induced pluripotent stem cells, preparation truncated recombinant histones, serotonylation happens at position 5 (Q5ser) H3 organisms make serotonin (Farrelly workers tissue nuclesosomes having trimethylated 4 (H3K4me3) leading formation H3K4me3Q5ser. latter molecule shows pattern mammalian tissues, brain gastrointestinal tract, both known large amounts serotonin.Studies across genome human serotonergic neurons, murine developing brain, cultured cells suggest H3K4me3Q5ser nucleosomes increased euchromatin, responsive differentiation associated Maze increases factor IID (TFIID) H3K4me3 augments (Girault, express ectopically mutant cannot serotonylated show markedly changed H3K3me3Q5ser-target loci, deficits Hence, inferred there direct role permissive different neurotransmission signalling.The same undergoes control during placental corresponds changes affect metabolic (Chan 2024). used transgenic mice depends uptake transporter (SERT). SERT deletion decreases enrichment genome, affects neurodevelopmental networks genes early embryonic tissues brain. authors these data placenta interface maternal physiology development foetal 2024).However, more research necessary completely determine how involvement modulates tissue-specific functions. Moreover, full catalogue their downstream effects neurodevelopment could explain unusual monoamine mechanisms risk disorders 2024).Histamine, involved monoaminylation. recently histaminylation catalysed occurs (Q5). H3Q5his antibody they produced validated concentrations synthesis histamine namely, tuberomammillary nucleus (TMN), according sleep-wake patterns. were affected drugs influence sleep "writer" an "eraser" "rewriter" H3. found, based several structural studies, reduces H3K4 methylation mixed lineage leukemia (MLL) complex (a family methyltransferases) (Zheng 2025).Monoaminylation investigated psychiatric disorders. after stress and/or antidepressant exposures. combination genome-wide studies dorsal raphe (DRN) male female subjected chronic social defeat stress, DRN patients major depressive disorder (MDD). effect exposure MDD association between H3K4me3Q5Ser related MDD. stress-induced MDD-linked (fluoxetine) exposures, viral-mediated therapy decrease levels study impact behaviour stress. influences transcriptional plasticity. Chronically-stressed abnormal activity DRN, antidepressant-and disruption this proving adequate behaviour. Corresponding patterns seen on-as compared off-antidepressant time death. antidepressant-associated separate neurotransmission, clinical drug 2024).Maze's discovered 2020 dopamine forms bonds H3Q5dop (Lepack Dopamine learning memory, reward, substance abuse, motor function Lepack (2020) liquid chromatography-mass spectrometry (LC-MS/MS) enzymatic assays serotonylation, dopaminylation catalyzed H3Q5, isolated (H3Q5dop) conjunction K4 trimethylation (H3K4me3Q5dop) correlates ventral tegmental area (VTA), region where behavioural decreased rat well post-mortem following continuous use cocaine. VTA dysregulation timing cocaine intake withdrawal.To better learn functional raised abstinence, delivered dominant viral vectors rats RNA-sequencing virally -affected reduced reverse normally observed withdrawal. addition, decreasing prevented cocaine-seeking -induced release accumbens, reward receives dopaminergic nerve supply VTA. findings suggested roles mediating independent occurrence vulnerability abuse relapse.In addition disorders, noted other cancer (Li Currently most commonly tail 2014), although it possible targeted.Modified pathogenesis (Panariello 2022). However, involve discussed preceding sections above review still very much infancy. evidence suggesting As sections, plays seeking contributes stress-and (fluoxetine)-mediated established modifications, disorders.There difficulties interpretation (Park 2022;Paul Potter, 2024): extreme complexity brain; temporal variations modifications; type; laboratory required; determining whether cause disease process.As mentioned, TGM2. Inhibitors targeting developed, encompassing irreversible types, undergoing trials conditions celiac sprue, neurodegenerative (Song 2017;Badarau 2015;Keillor Johnson, 2021). overall efficacy present psychotropic arguably no than ones introduced fifty years ago, improving outcomes (Paul urgently needed developments current article, is, TGM2, field neuroscience drugs. somewhat speculative, date, even preclinical (phase 0) not conducted area.Moreover, interconnected if abnormalities particular patient, likely (Aljabali 2024), compounding finding effective acting epigenetically treating

Language: Английский

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MicroRNAs: A Novel Approach for Monitoring Treatment Response in Major Depressive Disorder?

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(2), P. 21 - 21

Published: March 3, 2025

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders, with an increasing incidence each year and important socioeconomic burden. Although new treatments are continuously being developed, there no effective monitoring method to determine suitability treatment ensure positive outcomes. Therefore, patients often struggle ineffective antidepressants their potential adverse effects, which halts any future progress in managing disorder. Considering microRNAs (miRNAs) as biomarkers for various pathologies evidence modulation several genes involved MDD, this minireview aimed evaluate literature data on impact miRNAs MDD usefulness response. The correlations between expression support existence a common epigenetic mechanism explain differences influencing efficacy MDD.

Language: Английский

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Epigenetic regulation of stress

Progress in brain research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Epigenetic factors in posttraumatic stress disorder resilience and susceptibility

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

Published: March 20, 2025

Abstract Background Posttraumatic stress disorder (PTSD) affects approximately 8% of the US population, with varying susceptibility among individuals exposed to trauma. While genetic factors contribute PTSD risk, emerging evidence suggests that epigenetic mechanisms play a crucial role in translating environmental exposures into lasting neurobiological changes. Purpose This review provides comprehensive analysis cutting-edge research on PTSD, particular emphasis novel findings regarding resilience and mechanisms. We explore recent technological advances their applications understanding pathophysiology. Main body Advanced epigenomic approaches have revealed complex interactions between DNA methylation, histone modifications, non-coding RNAs PTSD. Novel highlight cell type-specific signatures temporal dynamics following trauma exposure. Single-cell studies identified previously unknown cellular heterogeneity responses. Recent data modifications not only influence individual but may also transgenerational transmission effects. Integrative multi-omics new insights molecular networks underlying vulnerability. Conclusion unprecedented complexity These open avenues for personalized interventions based profiles suggest therapeutic strategies targeting modifications. enhanced has significant implications risk assessment, prevention, treatment. Graphical abstract

Language: Английский

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Exploring the Potential of Precision Medicine in Neuropsychiatry: A Commentary on New Insights for Tailored Treatments Based on Genetic, Environmental, and Lifestyle Factors

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 371 - 371

Published: March 24, 2025

Neuropsychiatric disorders are complex conditions with multifactorial etiologies, in which genetics play a pivotal role. Despite significant advancements psychiatric research, traditional treatment options remain largely symptomatic, focusing on clinical signs without fully addressing the underlying biological causes. However, recent developments precision medicine—an approach that tailors treatments based genetic, environmental, and lifestyle factors—hold great promise for transforming of these disorders. By identifying specific genetic markers understanding gene–environment interactions, medicine can offer more personalized effective treatments, leading to better patient outcomes. Our primary aim was explore how integrating data environmental factors could enhance neuropsychiatric such as schizophrenia, bipolar disorder, depression. The secondary examine potential pharmacogenomics gene therapy improving therapeutic strategies. results indicate while progress has been made, challenges remain, including complexity interactions need granular phenotypic data. In conclusion, revolutionize by providing individualized care considers makeup, influences, factors, paving way therapies improved

Language: Английский

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Identification of Specific Plasma miRNAs as Potential Biomarkers for Major Depressive Disorder

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2165 - 2165

Published: Sept. 24, 2024

Backround: Depression is a significant concern in clinical and preclinical psychoneurobiological sciences due to its high prevalence individual collective consequences. Identifying efficient biomarkers for accurate diagnosis crucial, with ideal having detectable serum levels conformational thermal stability. This study aims identify stable plasma the prognosis of major depressive disorder, as pathogenesis disorder remains incompletely understood, affecting accuracy. Methods: Thus, this included ten MDD patients eight healthy controls. The present work analyzed miRNAs compared Results: Eleven specific miRNAs, particularly hsa-miR-874-3p; hsa-let-7d-5p; hsa-miR-93-3p showed upregulation-type variations group disorder. miRNA functionality linked pathophysiology. Conclusions: identifies “bouquet” upregulation suggesting further research determine their suitability personalization evaluation, ultimately becoming integral components depression serological evaluations.

Language: Английский

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Association between vitamin A intake and depression: A cross-sectional study of NHANES from 2005 to 2020 and Mendelian randomization analysis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Background: The association of vitamin A intake with depression remains unclear. This study combined observational research and Mendelian randomization (MR) analysis to explore the relationship between depression. Methods: First, we performed a cross-sectional utilizing National Health Nutrition Examination Survey (NHANES) data from 2005 2020. Weighted multivariable logistic regressions restricted cubic spline (RCS) regression were applied We also conducted stratified sensitivity analyses assess robustness results. Second, MR causal risk using publicly available Genome-Wide Association Studies (GWAS) database. The inverse-variance weighted (IVW) method was our primary for analysis. In addition, multiple evaluate reliability results, including Cochran’s Q test, MR-Egger intercept regression, MR-Pleiotropy Residual Sum Outlier (MR-PRESSO), leave-one-out Results: In study, total 38,157 individuals enrolled. negatively associated after adjusting all covariates (OR=0.92, 95%CI: 0.88-0.97, P=0.001). Similar inverse associations observed when converted into categorical variables. RCS found an L-shaped nonlinear dietary (P non-linearity=0.010) covariates. Vitamin consumption inversely (OR=0.999, 95% CI: 0.999-1.000, P=0.002) intakes below 492.00 μg. contrast, no (P=0.656) μg or higher. Furthermore, remained robust in both analyses. analysis, 15 single-nucleotide polymorphisms (SNPs) identified as instrumental variables (IVs). IVW significant (OR=0.39, 0.10-1.58, P=0.188). results method, median simple mode method. Sensitivity confirmed these Conclusions: that depression, regardless whether measured continuous variable. However, findings did not indicate risk.

Language: Английский

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