Biology subjects

Antczak, P.

Publications and source records attributed to Antczak, P..

3 recordsLinked to original sources

bioRxiv2026

Epigenetic changes induced by developmental PFAS exposure in zebrafish associate with behavioral alterations in unexposed offspring

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with documented toxic effects, yet their multi- and transgenerational impacts on neurodevelopment and underlying mechanisms remain poorly understood. Here, we present a comprehensive study delineating the effects of developmental exposure to environmentally relevant concentrations of PFOS and PFBS on behavior, transcriptome, and genome-wide DNA methylation patterns in the directly exposed generation (F0) and their unexposed offspring (F1 and F2) in zebrafish. Both PFOS and PFBS altered larval behavior, linked to transcriptomic and DNA methylation changes in neuro-related pathways, even in the unexposed offspring. Importantly, specific DNA methylation changes in F0 were associated with behavioral outcomes in F2 animals, suggesting that these alterations could underlie transgenerational effects. Pathways associated with differentially methylated genes were prominently enriched for response to light and circadian regulation. Our findings demonstrate that developmental exposure to PFAS causes transgenerational behavioral effects in zebrafish and suggest that epigenetic changes induced by direct exposure may serve as markers for predicting outcomes in subsequent, unexposed generations. TEASERPFAS induce circadian-related epigenetic changes in zebrafish associated with behavioral impacts in unexposed offspring.

molecular biology↗

bioRxiv2025

Nutrient stress activates Rab5b-mediated autophagy to remodel the synaptic proteome

Synaptic proteostasis is crucial for maintaining neuronal function and plasticity, yet how synapses adapt to metabolic stress remains poorly understood. Here, we show that nutrient deprivation, particularly serum withdrawal, induces robust autophagy-dependent remodeling of the synaptic proteome, while mTORC1 inhibition has more limited effects. Nutrient stress rapidly activates autophagy both globally and at synapses, with synaptic autophagy peaking within 1-2 hours of serum withdrawal. Mechanistically, we uncover that the LC3 lipidation complex (ATG5-ATG12-ATG16L1) is recruited to synapses via Rab5b-positive endosomes in a dynein-dependent manner. Live imaging reveals enhanced Rab5b-ATG16L1 co-trafficking and increased ATG5 mobility upon serum withdrawal, supporting a model of spatiotemporally controlled autophagy precursor delivery to synaptic compartments. Functionally, nutrient deprivation acutely dampens neuronal excitability in vitro, while a two-week fasting-mimicking diet in vivo triggers synaptic proteome remodeling that overlaps with starvation-induced autophagy cargo. In contrast, restriction of mTORC1-activating amino acids fails to induce comparable synaptic changes, suggesting that synaptic autophagy is regulated by nutrient signals beyond mTORC1. Our findings define a Rab5b-mediated trafficking mechanism that couples nutrient sensing to localized synaptic degradation, providing new insight into how neurons preserve proteostasis under metabolic challenge.

neuroscience↗

bioRxiv2023

Genetic variability in pathways associates with pesticide-induced nervous system disease in the United States

Nervous system disease development following pesticide exposure can vary in a population, but genetic susceptibility to chemicals is poorly characterized. We developed a framework to build Chemical - SNP (single nucleotide polymorphism) - Disease linkages via biological pathways. We integrated these linkages with spatialized pesticide application data for the United States from 1992 - 2018 and nervous system disease rates for 2018 to characterize genetic variability in pesticide-induced nervous system disease. We found that the number of SNPs implicated per pesticide in US states positively correlates with disease incidence and prevalence for Alzheimers disease, Parkinson disease, and multiple sclerosis. Further, only 2% of pesticide sets used together over time overlapped between high disease occurrence and low disease occurrence states, with more SNPs implicated in pathways in high disease occurrence states. This supports that pesticides contribute to nervous system disease, and we developed priority lists of SNPs, pesticides, and pathways for further study.

pharmacology and toxicology↗