Biology subjects

Hermanns, M.

Publications and source records attributed to Hermanns, M..

3 recordsLinked to original sources

bioRxiv2025

DNMT1 Coordinates PV Interneuron-Glia Coupling to Maintain Cortical Network Stability and Regulate Behavior

Parvalbumin (PV) interneurons are central to cortical network stability and psychiatric vulnerability. Here, we identify DNA methyltransferase 1 (DNMT1) as a key epigenetic regulator linking PV interneuron function to glial and extracellular matrix remodeling. Conditional PV-specific Dnmt1 deletion combined with single-cell RNA-seq, in vivo electrophysiology, histology, and behavioral analyses revealed that loss of DNMT1 increases PV spiking activity but reduces inhibitory efficacy, leading to network desynchronization and depression- and anxiety-like behavior in mice. These physiological alterations were accompanied by broad, non-cell-autonomous transcriptional changes in astrocytes and oligodendroglial populations, prominently affecting pathways involved in perineuronal-net (PNN) organization and neuron-glia communication. Cell-cell interaction analyses revealed disrupted NRXN-NLGN, TNR-integrin, and semaphoring signaling, consistent with weakened perisomatic adhesion and PNN integrity. Together, our findings demonstrate that DNMT1 maintains inhibitory circuit stability through cell-autonomous regulation of PV interneuron function, which secondarily shapes glial transcriptional states and extracellular scaffolds to preserve cortical network synchronization and emotional behavior.

neuroscience↗

bioRxiv2024

Dnmt1-deficiency in PV interneurons alters cortical circuit function and leads to depression-like behavior

Neuropsychiatric disorders, including major depressive disorder (MDD), are highly prevalent in modern society, arising from a complex interplay of genetic and environmental factors. Alterations in the function of cortical inhibitory GABAergic interneurons, along with dysregulations of epigenetic signatures and key regulators such as DNA methyltransferase 1 (DNMT1), have been implicated in these conditions. Through its role in catalyzing DNA methylation, DNMT1 modulates the synaptic activity of parvalbumin-expressing (PV) interneurons, which are essential for cortical inhibition. However, the functional consequences of DNMT1 activity in cortical interneurons at the network level and its impact on behavior remain unknown and must be explored to fully understand the disease implications of dysregulated DNMT1 expression and function. To address this, we utilized a conditional knockout mouse model with Dnmt1 deletion in PV interneurons. Our findings reveal that a Dnmt1 deficiency leads to increased spontaneous firing rates of cortical neurons, reduced cortical gamma oscillations, and altered visually evoked neural responses. Despite intact sensory perception, Dnmt1-deficient mice exhibited reduced physical activity, heightened anxiety-like behavior, and signs of anhedonia and apathy, which represent core features of MDD. These results underscore the critical role of DNMT1 in PV interneuron function and identify it as a potential target for MDD research.

neuroscience↗

bioRxiv2021

Allicin From Garlic Disrupts the Cytoskeleton in Plants

Allicin is a defence substance produced by garlic cells upon injury. It is a thiosulfinate showing redox-activity and a broad range of antimicrobial and biocidal activity. It is known that allicin efficiently oxidizes thiol-groups and it has been described as a redox toxin. In order to learn more about the effect of allicin on plants we used pure synthetized allicin, and investigated cytoplasmic streaming in sterile filaments of Tradescantia fluminensis, organelle movement using transgenic Arabidopsis with organelle-specifics GFP-tags, and effects on actin and tubulin in the cytoskeleton using GFP-tagged lines. Auxin distribution in roots was investigated using PIN1:GFP, PIN3:GFP, DR5:GFP and DII-VENUS Arabidopsis reporter lines. Allicin inhibited cytoplasmic streaming in T. fluminensis and organelle movement of peroxisomes and the Golgi apparatus in a concentration-dependent manner, inhibited root growth and destroyed the correct root tip distribution of auxin. We speculate that the cytoskeleton can be a primary "receptor" for allicins oxidizing properties and as a consequence cytoskeleton-dependent cellular processes are disrupted.

plant biology↗