Unit Brain Ingenium

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of biologically active molecules found in plastics, pesticides, and everyday products that can cause harmful effects on human health by interfering with hormone function. Humans are unavoidably exposed to these substances that leach from everyday products and enter the body mainly through contaminated food and beverages.

Great concern is arising about the detrimental effects of EDCs and the European Commission is strongly active in regulating products containing these chemicals. EDCs can contaminate soil and water, causing several diseases with consequent high social and economic burden.

Association studies suggest a link between exposure to EDC and the onset of neurodegenerative disorders. However, it is unclear which aspects of the human nervous system can be modified by EDCs; this represents a critical gap in the understanding of the mechanisms underpinning EDC-induced neurotoxicity.

Considering these alarming data, the UNIT BRAIN project was established. The Leading Principal Investigator (PI) of this project is Andrea Di Credico from the “G. D’Annunzio” University of Chieti-Pescara, member of the Cell Reprogramming and Differentiation Lab, led by Prof. Angela Di Baldassarre. The local PIs are Yaiza Potes, from the university of Oviedo, Lavinia-Eugenia Ferariu and Romeo Ciobanu from the Technical University of Iași.

In this project, human induced pluripotent stem cells (hiPSCs)-derived neurons and brain organoids will be used as a model to study the potential neurodevelopmental toxicity of EDCs, and the effect of a candidate to mitigate EDC activity. The interference of EDCs with neuronal biology will be studied using 2D neuronal cultures and brain organoids with an efficient interdisciplinary approach: high-content microscopy (HCM) will be used to monitor EDC-induced phenotypic modifications. Mitochondrial function, and autophagic machinery will be investigated. Also, the modality by which EDCs pass brain organoids blood-brain barrier will be explored. Relevant biological data will be used to classify the phenotypes of treated neurons and brain organoids through artificial intelligence (AI) methods.

This multidisciplinary approach will uncover new fundamental insights into how EDCs affect the human nervous system. The main objectives of this project are:

– To elucidate the effects of EDCs on human nervous system using cutting-edge human in-vitro models to increase the understanding of how EDCs could be involved in the etiology of neurodegenerative diseases.

– To test potential compounds to mitigate or reverse the adverse outcomes led by EDCs in human-derived neuronal models.

Our results will generate fundamental insights into the effect of the EDCs that humans are most exposed to, and the outputs will be crucial in improving the population’s health.

Feedback to healthcare decision-makers will be provided to implement adjustments in the regulation of the manufacturing of everyday products containing EDCs to minimize exposure to them.

The results could encourage the chemical industries to develop substitute to EDCs. The packaging industries could replace such materials with fewer toxic ones. These changes can reduce environmental pollution due to EDCs with benefits for the environment, human health and save economic resources for public health.

By uncovering the mechanisms through which EDCs influence human nervous system, the research will shed light on the interconnection between environmental factors and human health. This awareness promotes a cultural shift towards sustainable practices and environmental management. This project will also have a social impact: thanks to dissemination programs, general population will become aware of the health and environmental risks linked with the use of plastics.

Through dissemination activities dedicated to the general population, policymakers, and scientific audience, the communities will become aware of the risks linked with the use of plastics and ways to minimize exposure.

The engagement of policymakers will strengthen regulations on the use of EDCs. The translation of research into clinical practice will be favored by informing healthcare providers about the neurological effects of EDCs. This can lead to improved patient care through early diagnosis, and intervention. By pursuing these pathways, the results of the project can have a tangible and lasting impact.

To maximize the quality and impact of our research in alignment with the CoARA vision, the project environment will foster collaboration between researchers within the consortium from diverse disciplines. The partners will organize strategies to attract further funding and resource allocation to support follow-up studies. This includes securing funding from external sources and establishing partnerships. The results of the project will enhance innovation, excellence, collaboration, and scientific impact.

To ensure the long-term sustainability of the project, a collaborative framework will be established between INGENIUM partners.

The engagement with stakeholders (e.g., affected communities, policymakers) will be considered. In this way, the project can build support, and engagement. By implementing these strategies, the project will establish a solid foundation for long-term sustainability, impact, and relevance in addressing new critical scientific questions.

The success of such a ground-breaking approach is guaranteed by the integration of the different expertise. The proficiency in HCM and morphological analysis of the “G. D’Annunzio” University of Chieti-Pescara ensures precise characterization of cellular responses to EDCs, which combined with the expertise in mitochondrial and autophagy analyses of the University of Oviedo, and the in vitro investigation analysis of the BBB made by one of the Iași group, will generate biological data elucidating mechanisms of cellular dysfunction and toxicity that the other Iași group will use to train AI models to classify the EDC-induced phenotypic modifications. The complementary expertise and advanced methodologies of these consortium will ensure robust research outcomes and impact on the population and the environment as well.