Project description:Considering the present scenario of fast-paced life, the major shifts in eating culture in the last five decades, and the crucial role of smell in food intake, it is thus crucial to map and better understand the effects of ultra-processed diets - especially under short-term regimens - on our brain metabolism and sense of smell. To address this question, we used mice to investigate the effects of the short-term consumption of three diets varying in macronutrient composition and origin (one whole-grain-based and two ultra-processed synthetic diets) on the transcriptional profiles of the olfactory mucosa and different brain regions.
Project description:Considering the present scenario of fast-paced life, the major shifts in eating culture in the last five decades, and the crucial role of smell in food intake, it is thus crucial to map and better understand the effects of ultra-processed diets - especially under short-term regimens - on our brain metabolism and sense of smell. To address this question, we used mice to investigate the effects of the short-term consumption of three diets varying in macronutrient composition and origin (one whole-grain-based and two ultra-processed synthetic diets) on the transcriptional profiles of the olfactory mucosa and different brain regions.
Project description:3,3’,5.5’-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40μM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 μM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 μM. Interestingly, while continued 0.75- 48 hpf TBBPA exposures (10 μM) led to severely deformed embryos, replacing exposure solution with chemical-free media at 6 hpf mitigated this effect, with 100% normal embryos at 48 hpf. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we hypothesized that TBBPA inhibits histone acetylation, resulting in lack of open chromatin within promoters of zygotic genes and delaying ZGA. Therefore, we co-exposed embryos to 20 μM TBBPA and 100 μM N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTB co-exposures from 0.75- 3 hpf significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.
Project description:In this study, we differentiated mouse ESCs via 3D aggregates called embryoid bodies in presence of environmental and human relevant TBPPA concentrations for 28 days. We collected samples at different time points and analyzed TBBPA-dependent global gene expression changes by RNA-seq. Our analyses revealed a potential TBBPA multifaceted developmental toxicity with effects on the nervous and cardiac/skeletal muscle systems. Mechanistically, our findings suggest TBBPA endocrine disrupting activities in part via prolactin signaling.
Project description:Vertebrate eye devlopment is partially regulated by thyroid hormones. TBBPA is a chemical that interacts with thyroid receptors. We investigated the effects of TBBPA on eye development of zebrafish. We expected TBBPA exposure to cause transcriptional changes of visual-system-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Additionally, the reversibility of effects after recovery in clean water for three days was investigated.
Project description:A goldfish brain enriched cDNA combined with a carp microarray (Gracey et al., 2004). Female goldfish were i.p. injected with 1 ug/g muscimol once and after 6 hours, telencephalon dissected and used in microarray analysis. More details on microarray hybridizations and technique used in our laboratory in Martyniuk et al. Gene expression profiling in the brain of male goldfish exposed to 17α-EE2(paper under review) Keywords: muscimol, GABA, goldfish, brain
Project description:Taking into account the relevance of the smell sense in the early diagnosis of neurodegenerative diseases, we have analyzed the expression profile of the dark proteome across public proteomic and transcriptomic data derived from primary olfactory areas such as olfactory bulb (OB) and cleft mucus as well as from specific brain/OB cell linages. In this study, we have used an experimental workflow combining neuropathological diagnosis, co-regulation maps, physical and functional interaction data, transgenic models, intracellular and extracellular proteomics and immunohistochemical and biochemical approaches to partially decipher the UPE1 PITHD1 function in olfactory metabolism.