Biology subjects

Bonzanni, M.

Publications and source records attributed to Bonzanni, M..

4 recordsLinked to original sources

bioRxiv2026

Profiling Gingival Inflammation in a 3D Oral Tissue Model Reveals Early Features of Disease Progression

Gingival health depends on a balanced interplay among the gingival epithelium, immune system, and oral microbiome. Disruption of this equilibrium through sustained biofilm accumulation and host inflammatory responses leads to gingivitis, a highly prevalent yet reversible condition which if left untreated could progress into more severe and irreversible condition called periodontitis. The early onset of gingivitis remains poorly defined due to subtle clinical presentation and pronounced interindividual variability. Current diagnostic approaches rely largely on clinical assessment and endpoint biomarkers, limiting insight into the early host-microbiome interactions that drive disease initiation. Here, we employ a previously validated, physiologically relevant oral tissue model (OTM) to longitudinally investigate epithelial-microbiome interactions following inoculation with patient-derived dysbiotic microbiomes from early-stage gingivitis. The OTM maintained host tissue integrity and microbial viability over a seven-day period, preserving epithelial barrier function, dynamic inflammatory responses, and disease-associated microbial signatures. Notably, we establish, for the first time in an in vitro platform, clinical calibration against gingival crevicular fluid (GCF), demonstrating that OTM responses recapitulate inoculum-dependent inflammatory signatures, increased microbial dissimilarity under dysbiotic conditions, and coordinated host-microbiome metabolic interactions. While pro-inflammatory responses were most pronounced at early time points, subsequent modulation toward anti-inflammatory states highlights the temporal complexity of host responses and suggests that longer culture durations may further resolve disease trajectories. Collectively, these findings validate the OTM as a robust, physiologically relevant platform that captures key features of periodontal health and inflammation. By integrating host viability, microbial ecology, and clinical benchmarking, this system enables mechanistic interrogation of early disease-driving processes and provides a translational framework for advancing predictive diagnostics and preventive therapeutic strategies in periodontal disease.

microbiology↗

bioRxiv2025

Reframing Sleep Architecture: A Compositional and Temporal Approach to Sleep Data Analysis

Significant progress has been made in developing sleep staging methodologies; however, less attention has been devoted to the analysis of sleep architecture. Two critical aspects remain underexplored: the choice of binning window (i.e., grouping data into time intervals) and the statistical treatment of the interdependencies among sleep phases. While one-hour bins are commonly used, this choice is often based on convention rather than empirical justification. Additionally, sleep architecture data are typically expressed as proportions of time spent in each sleep phase, forming compositional datasets, non-negative values that represent parts of a whole and are constrained by a constant sum (e.g., 100%). Such data violate the assumptions of traditional statistical methods, yet their compositional nature is often overlooked, compromising analytical validity. In this study, we address two key methodological challenges in sleep architecture analysis: (1) determining the optimal binning window through a data-driven approach that balances information retention and noise reduction, and (2) applying isometric log-ratio (ILR) transformation to account for the compositional structure of the data, enabling the use of conventional statistical tests. By addressing these issues, we propose a more rigorous and interpretable framework for analyzing sleep architecture, aiming to enhance the accuracy and reproducibility of findings in sleep research. Statement of SignificanceSleep architecture is typically analysed without accounting for the interdependent nature of sleep stages, leading to potentially misleading interpretations. This study introduces a compositional analytical framework that treats sleep data as interdependent, where changes in one phase necessarily impact the others. By integrating compositional data principles with a biologically grounded approach to temporal binning, we offer researchers a practical and interpretable method for analysing sleep structure. This work challenges conventional analysis practices and encourages a rethinking of how sleep-related biological questions are framed. These findings hold potential relevance for improving the design and interpretation of both experimental and clinical sleep studies, ultimately supporting more accurate insights into physiological and pathological studies involving altered sleep patterns.

neuroscience↗

bioRxiv2024

Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer's disease.

The diseases trajectory of Alzheimers disease (AD) is associated with and worsened by hippocampal hyperexcitability. Here we show that during the asymptomatic stage in a knock in mouse model of Alzheimers disease (APPNL-G-F/NL-G-F; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal activity. Our results demonstrated that neuronal hyperexcitability during the asymptomatic stage of a KI model of Alzheimers disease originated at the synaptic compartment and is associated with adenosine deficient tone. These results extend our comprehension of the hippocampal vulnerability associated with the asymptomatic stage of Alzheimers disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/590882v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@cd128forg.highwire.dtl.DTLVardef@17d7701org.highwire.dtl.DTLVardef@100337org.highwire.dtl.DTLVardef@14333d0_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LISynaptic hyperexcitability spreads to the soma and manifests at low frequencies of stimulation C_LIO_LISynaptic hyperexcitability is associated with reduced adenosine tone in vitro and in vivo C_LIO_LIReduced adenosine tone is driven by reduced ATP-to-adenosine extracellular conversion C_LIO_LIRestoration of adenosine tone successfully normalizes neuronal excitability in the AD model C_LI

neuroscience↗

bioRxiv2019

Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential

All cells possess an electric potential across their plasma membranes. While familiar in the context of excitable cells such as neurons, healthy non-excitable cells are also able to generate and receive bioelectric signals. The cellular resting membrane potential (RMP) regulates many factors in cell homeostasis, such as cell proliferation, differentiation and apoptosis. It is therefore critical to develop simple strategies to measure, manipulate and characterize this feature. Current studies to evaluate RMP rely on the patch clamp approach, which is technically challenging, low-throughput and not widely available to the scientific community. Here, we present a relatively simple methodology to functionally study the role of RMP in non-excitable cells by modulating it pharmacologically, and using a voltage-sensitive dye to characterize the contribution of individual ions to the RMP. Specifically, we define protocols for using extracellular solutions in which permeable ions (Na+, Cl- and K+) are substituted with non-permeable ions (N-Methyl-D-glucamine (NMDG), gluconate, choline, SO42-) to study and manipulate RMP in vitro. The resulting RMP modifications were assessed with both patch clamp and a voltage sensitive dye. Using an epithelial and cancer cell line, we demonstrate that the proposed ionic solutions can determine the relative contribution of ionic species in setting the RMP and be used to actively and selectively modify the RMP. The proposed method is simple and reproducible and will make the study of bioelectricity more readily available to the cell biology community by enabling functional modulation of RMP in most cellular assays.\n\nAuthor Disclosure StatementsNo competing financial interests exist.

cell biology↗