Biology subjects

Demeter, K.

Publications and source records attributed to Demeter, K..

5 recordsLinked to original sources

bioRxiv2026

Targeting microglial P2Y12-receptor signalling attenuates neurodegeneration in experimental Parkinsons disease

Neuroinflammation is increasingly recognized as a determinant of dopaminergic neuron vulnerability in Parkinson's disease, yet the receptor-level mechanisms linking microglia to disease progression remain incompletely defined. We investigated whether microglial P2Y12 receptor (P2Y12R) signalling drives neurodegeneration in experimental Parkinsonism and assessed its pharmacological tractability. Tamoxifen-inducible microglia-specific P2ry12 deletion was examined in acute and subchronic MPTP models, with receptor deletion induced before or during disease progression. Neurodegeneration, neuroinflammation, neurochemistry, and motor function were evaluated, and novel P2Y12R antagonists identified by structure-based virtual screening were characterized in vitro and following central administration in vivo. Inducible microglia-specific P2Y12R deletion reduced nigrostriatal dopaminergic neuron loss, preserved dopamine synthesis, attenuated acute and sustained neuroinflammatory responses, and improved parkinsonian motor deficits without affecting survival. Importantly, delayed receptor deletion during ongoing neurodegeneration remained protective, indicating that P2Y12R contributes to disease progression. Two novel antagonists exhibited functional P2Y12R inhibition in vitro, and central administration of the most promising candidate recapitulated the neuroprotective phenotype observed following genetic receptor deletion. These findings identify microglial P2Y12R as a therapeutically relevant regulator of neuroinflammation and dopaminergic vulnerability and provide complementary genetic and pharmacological proof-of-concept for targeting central P2Y12R in Parkinsonism.

neuroscience↗

bioRxiv2025

Bacterial diversity turnover estimates in a continental river system

Understanding bacterial dynamics in large river systems is crucial for predicting continental-scale ecological functioning under anthropogenic pressures. Here, two consecutive surveys 6-years apart along the 2600 km Danube River found that carbon incorporation per cell and hour decreased by 5000 atoms every kilometer and that cells multiplied five times during their travel down the entire river. Resolving these cell turnovers taxonomically revealed taxa with a hundredfold difference from these average numbers. Bacterial community turnover was due to replacement (phylotype turnover) and could be linked to species sorting. This was despite an overall decrease in diversity richness downstream. Using linear models, we were able to relate carbon, cell, phylotype and diversity turnover rates to water residence time and discharge with outliers associated with human impacts. As such the reproduceable macroecological models predict microbial changes from anthropogenic and climate alterations along a continental drainage system providing insights into their ecological consequences.

microbiology↗

bioRxiv2024

Pretrauma cognitive traits predict trauma-induced fear generalization and associated prefrontal functioning in a longitudinal model of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that develops in susceptible individuals exposed to traumatic stress, challenging clinicians to identify risk factors and mechanisms for mitigating vulnerability. Here we investigated behavioral predictors of high fear generalization, a core PTSD symptom, and its neural correlates longitudinally in rats. In a comprehensive behavioral test battery of emotional and cognitive function, pretrauma lower operant learning performance emerged as high predictor of fear generalization following trauma. Posttrauma operant training facilitated fear extinction, suggesting an overlap in neural circuits governing operant learning and fear expression. Neuronal activity mapping revealed significant changes in the medial prefrontal cortex (mPFC) in high fear generalizers, with alterations in CRH/VIP+ interneuron functioning. Silencing prefrontal Crh expression after fear memory consolidation enhanced mPFC activation and reduced fear expression, favoring resilience. These findings highlight operant learning and mPFC alterations as vulnerability markers and mediators of excessive fear generalization, with implications for prevention and targeted therapy in PTSD.

neuroscience↗

bioRxiv2019

Implementation and Integration of Microbial Source Tracking in a River Watershed Monitoring Plan

Fecal pollution of water bodies poses a serious threat for public health and ecosystems. Microbial source tracking (MST) using host specific bacteria are used to track the source of this potential pollution and be able to perform a better management of the pollution at the source. In this study we tested 12 molecular MST markers to track human, ruminant, sheep, horse, pig and gull pollution to determine their usefulness in their application for an effective management of water quality. First, the potential of the selected markers to track the source was evaluated using fresh fecal samples. Subsequently, we evaluated their performance in a catchment with different impacts, considering land use and environmental conditions. All MST markers showed high sensitivity and specificity, although none achieved 100% for both. Although some of the MST markers were detected in hosts other than the intended ones, their abundance in the target group was always several orders of magnitude higher than in the non-target hosts, demonstrating their suitability to distinguish between sources of pollution. The MST analysis matched the land use in the watershed allowing a very accurate assessment of the main hazards and sources of pollution, in this case mainly human and ruminant pollution. Correlating environmental parameters like temperature and rainfall with the levels of the MST markers provided insight into the dynamics of the pollution along the catchment. The levels of the human associated marker showed a significant negative correlation with rainfall in human polluted areas suggesting a dilution of the pollution, whereas at agricultural areas the ruminant marker increased with rainfall. There were no seasonal differences in the levels of human marker, indicating human pollution as a constant pressure throughout the year, whereas the levels of the ruminant marker was influenced by the seasons, being more abundant in summer and autumn. Performing MST analysis integrated with land uses and environmental data can improve the management of fecal polluted areas and set up good practices.

ecology↗

bioRxiv2018

The swimming plus-maze test: a novel high-throughput model for assessment of anxiety-related behaviour in larval zebrafish. (Danio rerio)

Larval zebrafish (Danio rerio) has the potential to supplement rodent models due to the availability of resource efficient methods implying high-throughput screening and high-resolution imaging techniques. Although behavioural models are available in larvae, only a few, insensitive approaches can be employed to assess anxiety. Here we present the swimming plus-maze (SPM) test paradigm to assess anxiety-related states in young zebrafish. The \"+\" shaped apparatus consists of arms of different depth representing differentially aversive context. The paradigm was validated i.) in larval and juvenile zebrafish, ii.) after administration of compounds affecting human anxiety and iii.) in differentially aversive experimental conditions. Furthermore, we compared the SPM with conventional \"anxiety tests\" of larvae such as the open tank and light/dark tank tests to identify their shared characteristics. We clarified that the preference towards deeper water is conserved trough the ontogenesis and can be abolished by anxiolytic or enhanced by anxiogenic agents, respectively. The behavioural read-out is insensitive to the aversiveness of the platform and unrelated to behaviours assessed by conventional tests utilizing larval fish. Taken together, we developed a sensitive high-throughput test measuring anxiety-related responses of larval zebrafish, which likely reflect bottom-dwelling behaviour of adults, potentially supporting larva-based integrative approaches.

animal behavior and cognition↗