Biology subjects

Bencsik, N.

Publications and source records attributed to Bencsik, N..

6 recordsLinked to original sources

bioRxiv2026

Investigation of autophagy-activating molecules in a glia-specific Spinocerebellar ataxia type model

Autophagy is a critical neuroprotective mechanism, the impairment of which can lead to severe neurodegenerative diseases. Spinocerebellar ataxia type 1 (SCA1) is a monogenic neurodegenerative disorder, characterised by the presence of protein aggregates and consequent loss of cellular functions. The expression of mutant Ataxin1 (ATXN1) in glial cells has been demonstrated to induce inflammatory responses and loss of supportive functions, thereby exacerbating neuronal degeneration in SCA1. Autophagic dysfunction has been shown to affect both neurons and glial cells, resulting in widespread pathological consequences. In this work, we aimed to evaluate the efficacy of two small-molecule autophagy activators, AUTEN-67 and AUTEN-99, in models of glia-specific SCA1 in Drosophila. Our results demonstrate that AUTEN-99 has a stronger autophagy enhancing effect, with significantly improved response times and survival rates, compared to untreated ATXN1 mutants. Glia-specific assays in mouse primary hippocampal cultures also confirmed that AUTEN-99 is a more effective activator. Ultimately, co-treatment of neuronal and glial cultures did not reveal any synergistic benefits from combining the two AUTEN compounds compared to single-agent treatment. Our findings contribute to a better understanding of the utility of AUTENs and may help to understand the critical role of autophagy in neurodegenerative diseases.

cell biology↗

bioRxiv2025

Postpartum enhancement of spatial learning and cognitive flexibility: an IntelliCage study

The transition to motherhood has been shown to result in significant changes in the structure and function of the brain, with particular emphasis on the enhancement of cognitive abilities that are essential for survival. Specifically, in murine models, spatial learning and cognitive flexibility have been identified as critical components of mothering. These abilities facilitate efficient navigation of the environment, resource acquisition, and responsiveness to offsprings needs. While cognitive enhancements during the postpartum period have been observed in various experimental setups, research using long-term data collection with automated monitoring in home cage setup is completely lacking even though it provides a more reliable approach than other experimental procedures. This study aims to address this knowledge gap by systematically examining spatial learning and cognitive flexibility in female mice during the reproductive stages using IntelliCage, with the objective of offering a more comprehensive understanding of maternal cognitive adaptations. Utilising the IntelliCage system, we observed that female mice in the postpartum phase outperformed pregnant and nulliparous females in place learning, reversal learning, and fixed schedule drinking tasks, demonstrating faster adaptation and superior retention of information. These paradigms mirror real-world challenges faced by mothers, such as navigating resources and balancing caregiving with self-maintenance. The enhanced performance demonstrated by the mothers could be attributed to their heightened motivation and cognitive abilities, potentially influenced by substantial hormonal shifts, which have been known to modify neuroplasticity in critical brain regions. The identification of these improvements in maternal behaviour may offer novel insights into the impact of reproductive experiences on brain function, with implications for maternal health and broader cognitive research.

neuroscience↗

bioRxiv2025

Glia cells are selectively sensitive to nanosized titanium dioxide mineral forms

Nanosized titanium dioxide is widely used by the industry e.g. in pigments, suncreams and food colors. Its environmental and biological effects have been investigated in the past, however, few studies have focused on its crystal structure-specific effects. In our experiments, the toxicity of two types of nanoparticles was examined on primary neural cultures with different cell-compositions, using MTT and LDH assays. Primary murine cell cultures containing only astroglia cells originated from two brain regions, as well as mixed neurons and glia cells or microglia cells exclusively, were treated with anatase and rutile TiO2 nanoparticles at varying concentrations for 24 or 48 hours. Our results show that neither anatase nor rutile nanoparticles reduced viability in cell cultures containing a mixture of neurons and glial cells, independently of the applied concentration and treatment time. Rutile but not anatase form induced cell death in cortical astroglia cultures already at 24 hours of treatment above 10 {micro}g/mL, while hippocampus-derived glial cultures were much less sensitive to rutile. The rutile form also damaged microglia. These findings suggest that products containing rutile-form nano-titanium particles may pose a targeted risk to astroglia and microglial cells in the central nervous system.

neuroscience↗

bioRxiv2024

Cell-type specific effects of Fusarium mycotoxins on primary neuronal and astroglial cells

Fumonisin B1, deoxynivalenol (DON) and zearalenone (ZEA) are toxic secondary metabolites produced by Fusarium molds. These mycotoxins are common food and feed pollutants and represent a risk for human and animal health. Although the mycotoxins produced by this genus can cross the blood-brain-barrier (BBB) in many species, their effect on neuronal function remains unclear. We investigated cell viability effects of these toxins on specified neural cell types, including mouse primary neuronal, astroglial and mixed cell cultures 24 or 48 hours after mycotoxin administration. Cell viability assay revealed that DON decreased cell viability in a dose-dependent manner, independently from the cultures type. Fumonisin B1 increased cell viability significantly on astroglial and mixed cell cultures in lower doses, while it exerted a highly toxic effect in 50 {micro}M. ZEA had significant effects on all culture type in 10 nM by increasing the cell viability. Since ZEA is a mycoestrogen, we analyzed the effects of ZEA on the expression of estrogen receptor isotypes ER and ER{beta} and mitochondrial voltage-dependent anion channel (VDAC1) by qRT-PCR. In neuronal and mixed cultures, ZEA administration decreased ER expression, while in astroglial cultures, it induced the opposite effect. ER{beta} and VDAC1 expression was not altered by ZEA in either culture types. ZEA also affected the firing pattern of neurons by enhancing the burst frequency. Our results demonstrate that Fusarium mycotoxins are acting on a cell specific manner in the brain tissue.

neuroscience↗

bioRxiv2023

Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells

Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of neuronal development and diseases. However, multiple studies have also demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of neurons derived from iPSCs. In this study, we conducted a comprehensive analysis of the h-iPSC-Ns via electrophysiological and microscopic techniques to follow their functional development at the cellular and network levels. This enabled us to provide a thorough description of the maturation process of h-iPSC-Ns over a 10-week period in vitro. Specifically, we have used conventional whole-cell patch-clamp and dynamic clamp techniques, alongside morphometry, to assess the characteristics of maturing h-iPSC-Ns. Additionally, we utilized calcium imaging to monitor the progression of synaptic activity and network communication. At the single cell level, human neurons exhibited gradually decreasing membrane resistance in parallel with improved excitability by 5 weeks of maturation. Their firing profiles were consistent with those of mature regular firing type of neurons. At the network level we observed the development of abundant fast glutamatergic and depolarizing GABAergic synaptic connections together with synchronized network activity. The identified sequence of differentiation events are consistent and offers a robust framework for developing targeted experiments at varying stages of neuronal maturation. This framework allows for the use of different, age-related methodologies or a singular set of experiments for a cultures maturation.

neuroscience↗

bioRxiv2020

PKD promotes activity-dependent AMPA receptorendocytosis in hippocampal neurons

AMPA type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the Protein Kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their co-localization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

neuroscience↗