Biology subjects

Nehls, S.

Publications and source records attributed to Nehls, S..

3 recordsLinked to original sources

bioRxiv2026

Longitudinal blood DNA methylation profiling reveals disrupted immune-epigenetic adaptation and candidate stress related loci in postpartum depression

Postpartum depression (PPD) arises during a period of profound endocrine and immune reorganisation, yet it is unclear whether women who develop PPD show distinct trajectories of immune-related DNA methylation compared to euthymic mothers. In a longitudinal cohort, women with PPD (n = 17) and healthy postpartum controls (n = 24) were followed from birth to 12 weeks postpartum, with repeated assessment of depressive symptoms and perceived stress and whole-blood sampling at 2-3 days (T0) and 12 weeks (T4) for Infinium MethylationEPIC array profiling. Healthy postpartum women showed a widespread gain in DNA methylation from T0 to T4 with strong enrichment of genes involved in neutrophil activation, chemokine signalling and interleukin-1 production, consistent with a normative immune-epigenetic down-tuning after childbirth. Women with PPD also exhibited immune-related changes, but with fewer differentially methylated CpGs and increased variance at sites that were stably hypermethylated in controls, indicating an attenuated and more heterogeneous epigenetic response. Although no CpG reached epigenome-wide significance in direct case-control contrasts, longitudinal consistency analyses highlighted a small set of CpGs with reproducible PPD-associated hypermethylation in stress- and signalling-related genes, including FKBP5 and AVP, suggesting that disrupted immune-epigenetic adaptation and altered regulation at these loci may contribute to postpartum vulnerability.

molecular biology↗

bioRxiv2023

Temporal dissociation between local and global functional adaptations of the maternal brain to childbirth: A longitudinal assessment

The maternal brain undergoes significant reorganization during birth and the postpartum period. However, the temporal dynamics of these changes remain unclear. Using resting-state functional magnetic resonance imaging, we report on local and global brain function alterations in 75 mothers in their first postpartum week, compared to 23 nulliparous women. In a subsample followed longitudinally for the next six months, we observed a temporal and spatial dissociation between changes observed at baseline (cluster mass permutation: pFWE < .05). Local activity and connectivity changes in widespread neocortical regions persisted throughout the studied time period (ANCOVAs vs. controls: pFDR < .05), with preliminary evidence linking these alterations to behavioral and psychological adaptations (interaction effect with postpartum time: uncorrected p < .05). In contrast, the initially reduced whole-brain connectivity of putamen-centered subcortical areas returned to control levels within six to nine weeks postpartum (linear and quadratic mixed linear models: pFDR < .05). The whole-brain spatial colocalization with hormone receptor distributions (Spearman correlations: pFDR < .05) and preliminary blood hormone associations (interaction effect with postpartum time: uncorrected p < .05) suggested that the postpartum restoration of progesterone levels may underlie this rapid normalization. These observations enhance our understanding of healthy maternal brain function, contributing to the identification of potential markers for pathological postpartum adaptation processes, which in turn could underlie postpartum psychiatric disorders.

neuroscience↗

bioRxiv2023

Proteins differentially expressed between pathogenic and non-pathogenic Entamoeba histolytica clones influence pathogenicity by different mechanisms

Recently, two genes involved in pathogenicity in a mouse model of amoebic liver abscess were identified based on their differential expression between non-pathogenic (A1np) and pathogenic (B2p) clones of the Entamoeba histolytica isolate HM:1-IMSS. While overexpression of a gene encoding the metallopeptidase EhMP8-2 decreases the virulence of the pathogenic clone B2p, overexpression of the gene ehi_127670 (ehhp127), encoding a hypothetical protein, increases the virulence of the non-pathogenic clone A1np, while silencing this gene in B2p decreases virulence. To understand the role of both molecules in determining the pathogenicity of E. histolytica, silencing and overexpression transfectants were characterized in detail. Silencing of ehmp8-2, of the homologous gene ehmp8-1, or of both together in A1np trophozoites significantly altered the transcript levels of 60-350 genes. This strong change in the expression profile caused by the silencing of ehmp8-1 and/or ehmp8-2 implies that these peptidases regulate expression of numerous genes. Consequently, numerous phenotypic characteristics including cytopathic, hemolytic and cysteine peptidase activity were changed in response to their silencing. Silencing of ehhp127 in B2p trophozoites did not affect other genes, whereas overexpression in A1np trophozoites results in an altered expression of approximately 140 genes. EhHP127 appears to be important for trophozoite movement, as silencing negatively affects and overexpression positively affects trophozoite motility. Interestingly, the specific silencing of ehhp127 also impairs cytopathic activity, cysteine peptidase and hemolytic activity. All three molecules of interest, namely EhMP8-1, EhMP8-2, and EhHP127 can be detected in amoeba vesicles. Our results clearly show that the proteins studied here influence the pathogenicity of amoebae in different ways and use entirely different mechanisms to do so. Author summaryThe human pathogen Entamoeba histolytica can live asymptomatically in the intestine or become invasive and cause fatal liver abscesses. Approximately 15,000 people die each year as a result of an amoebic infection. Recently, two clones with different pathogenicity (A1np: non-pathogenic; B2p: pathogenic) derived from the E. histolytica isolate HM:1-IMSS were compared at the transcriptome level. Two highly differentially expressed genes (ehhp127 encoding a hypothetical protein and ehmp8-2 encoding a metallopeptidase) were identified. Analysis of E. histolytica transfectants showed that silencing of ehhp127 and overexpression of ehmp8-2 in B2p trophozoites reduced amoebic liver abscess formation in the mouse model. In this study, we characterized E. histolytica silencing and overexpression transfectants of ehmp8-2, as well as of the homologous gene ehmp8-1 and of ehhp127. It was shown that the altered expression of the metallopeptidase genes has a strong influence on the expression of a large number of genes and that the phenotype is strongly altered as a result. Silencing of ehhp127 does not affect the overall expression profile. However, specific silencing has a negative effect on motility, cysteine peptidase, hemolytic and cytopathic activity. All three molecules were shown to be localized in trophozoite vesicles.

cell biology↗