Biology subjects

Landgraf, N.

Publications and source records attributed to Landgraf, N..

4 recordsLinked to original sources

bioRxiv2026

Axonal Branch Points of Parvalbumin Interneurons are Focal Sites of Tau-Induced Degeneration

Tau aggregation, a defining feature of tauopathies, commonly appears as neuropil threads within neurites including axons. However, the affected neuronal populations and the spatial organization of axonal vulnerability remain poorly defined. Here, following identification of Tau accumulation in parvalbumin (PV) interneuron axons in primary tauopathy patients, we generated a P301S Tau model targeted to PV interneurons to track the structural integrity of their neurites and somas. We observed neuronal loss alongside axonal dystrophy, with focal swellings forming preferentially at axonal bifurcations. This spatial enrichment exceeded chance levels, and local axonal geometry predicted swelling localization. Longitudinal in vivo imaging revealed that bifurcation-associated swellings progressed to axonal severing. Analogous bifurcation-associated dystrophies were present in PV axons in human primary tauopathy tissue. These findings indicate that axonal branch geometry shapes the spatial pattern of Tau-induced neurodegeneration and identify PV axonal branch points as sites of pathology in mouse and human tauopathy.

neuroscience↗

bioRxiv2025

Hepatocyte-like cells die via steroid hormone and nuclear receptor E75-mediated apoptosis

Metabolic organs must sustain physiological function while retaining the capacity for timely cell death. Systemic hormones play a key role in coordinating this balance, yet how they regulate cell death in vivo remains unclear. Here, we investigate hormone-regulated cell death in a metabolically specialised organ using Drosophila oenocytes, polyploid hepatocyte-like cells, as a tractable in vivo model. Using non-invasive longitudinal live imaging combined with oenocyte-specific genetic manipulation, we directly visualise larval oenocyte death during metamorphosis. We show that larval oenocyte loss is a dynamic, multistep process controlled by the steroid hormone ecdysone. We further identify the ecdysone-induced nuclear receptor E75 as a key regulator of the timing of cell death, as loss of E75 triggers premature oenocyte death. Oenocyte-specific manipulation of cell death pathways, together with live imaging using genetically encoded caspase reporters, provides direct evidence that larval oenocytes die by apoptosis. Together, this work defines how systemic hormonal signals regulate the timing of apoptosis in metabolically specialised polyploid cells and establishes oenocytes as a powerful in vivo system for studying cell death in metabolic organs.

developmental biology↗

bioRxiv2025

NEUROGLIAL CB1 RECEPTORS CONTROL NAVIGATION STRATEGIES

Navigation and memory functions are essential for survival and are regulated by the hippocampus. These processes are tightly controlled, and one of the key modulators involved is the endocannabinoid system, particularly through the cannabinoid receptor type-1 (CB1). CB1 is widely expressed in various hippocampal cell types. While it is known that CB1 participates in memory processes, its specific roles in different cell types and how these roles may differ between sexes remain unclear. This study investigates how CB1 signaling in the hippocampus, in both, cell-type-specific and sex-dependent manner, contributes to navigation and memory. To this end, we selectively deleted CB1 receptors from neurons, CAMKII-expressing neurons, and astrocytes from the hippocampus of adult male and female mice. We then assessed its effect on a broad range of behaviors, including innate emotional responses, memory, navigation, and other hippocampus-related functions such as nesting. Deletion of CB1 in CAMKII-expressing neurons produced a pronounced effect in males, leading to increased anxiety and impairments in both reference and spatial memory. These mice also showed altered performance in the Barnes maze, relying less on spatial strategies. By contrast, females were less affected by this specific deletion. Interestingly, only deletion of CB1 from astrocytes led to spatial memory impairments in females, which also showed reduced LTP and a decreased reliance on spatial strategies in the Barnes maze. In conclusion, our findings show that neuronal CB1 receptors are critical for the spatial navigation strategy in males, while astrocytic CB1 receptors play a key role in memory processes both in males and females.

neuroscience↗

bioRxiv2022

Photodynamic inactivation of pathogenic bacteria on human skin by applying a potent photosensitizer in a hydrogel

The antibiotic crisis increasingly threatens the health systems world-wide. Especially as there is an innovation gap in the development of novel antibiotics, treatment options for bacterial infections become fewer. The photodynamic inactivation (PDI) of bacteria appears to be a potent, new technology that may support the treatment of colonized or infected skin. In photodynamic inactivation, a dye - called photosensitizer - absorbs light and generates reactive singlet oxygen. This singlet oxygen is then capable of killing bacteria independent of species or strain and their antibiotic resistance profile. In order to provide a practical application for the skin surface, the photosensitizer was included in an aqueous hydrogel (photodynamically active hydrogel). The efficacy of this gel was initially tested on an inanimate surface and then on the human skin ex vivo. NBTC staining and TUNEL assays were carried out on skin biopsies to investigate potential harmful effects of the surface PDI to the underlying skin cells. The photosensitizer in the gel sufficiently produced singlet oxygen while showing only little photobleaching. On inanimate surfaces as well as on the human skin, the number of viable bacteria was reduced by over or nearly up to 4 log10 steps, equal to 99.99% reduction or even more. Furthermore, histological staining showed no harmful effects of the gel towards the tissue. The application of this hydrogel represents a valuable method in decolonizing human skin including the potential to act against superficial skin infections. The presented results are promising and should lead to further investigation in a clinical study to check the effectivity of the photodynamically active hydrogel on patients.

microbiology↗