Neurotoxicology

MALDI imaging (avbildande masspektrometri)

Description

Developmental neurotoxicology 1. Project manager: Sonja Buratovic.

Present information about interactive effects between radiation and pharmaceuticals is insufficient but has significant implications for protection of the developing neonate/child from adverse or harmful neurobiological effects following diagnostics or radiotherapy.

With the neonatal mouse, we can model a developmental period equivalent to the first 3 years in humans. The developmental processes occurring during this period are conserved between mammals and include maturation of neurons and glia as well as tightly regulated ontogenetic patterns of functional units in neurotransmitter systems. Methods aimed at investigating molecular initiating events, cellular effects and cognitive phenotypes, i.e., transcriptomics, epigenetics and behavioural tests are utilized in the lab. Current studies include investigations of interaction effects between anaesthetics/analgesics and low-doses of ionizing radiation.

By extending our knowledge of the causative mechanistic factors we are able to provide a first step to safer diagnostic/therapeutic modalities, applied in the paediatric clinic and also provide insights into the adverse outcome pathways for radiation and/or pharmaceuticals to possibly be utilized in the risk-benefit assessment in clinical practice.

Developmental neurotoxicology 2. Project manager: Diana-Ioana Lupu.

This research project focuses on the critical field of developmental neurotoxicity, specifically examining how endocrine-disrupting chemicals impact brain development. Endocrine disruptors are chemicals that interfere with the hormonal systems regulating various bodily functions, including growth, metabolism, and neural development. These disruptions can be particularly harmful during early stages of brain development when hormonal signaling is essential for the proper formation of neural circuits.

The research project is aimed at understanding the pathways through which these endocrine disruptors exert their toxic effects, and how they can compromise neurodevelopment. A central aspect of this work is the development of Adverse Outcome Pathways (AOPs), a framework used to describe the progression of toxicological effects from a molecular initiating event to adverse outcomes at the individual or population level. By mapping these pathways, we seek to bridge the gap between chemical exposures and their downstream neurodevelopmental consequences.

  • Buratovic S., Phillippot G., Stnerlöw B, Lönnqvist P.A. (2024) Exposure to lidocain in early life does not cause negative long-term behavioural changes in mice. Basic Clin. Pharmacol. Toxicol.; 135(2): 210 – 216.
  • Philippot G, Hosseini K, Yakub A, Mhajar Y, Hamid M, Buratovic S, Fredriksson R. (2022) Paracetamol (Acetaminophen) and its effect on the developing mouse brain. Frontiers in Toxicology. 4:867748
  • Buratovic S,Stenerlöw B, Sundell-Bergman S, Fredriksson A, Viberg H, Gordh T and Eriksson P. (2018) Effects on adult cognitive function following neonatal exposure to clinically relevant doses of ionizing radiation and ketamine in mice. British Journal of Anaesthesia. 120: 546-554.
  • Lupu D.I., Cediel Ulloa A., Rüegg J.; Endocrine-Disrupting Chemicals and Hippocampal Development: The Role of Estrogen and Androgen Signaling. (2023) Neuroendocrinology; 113 (12): 1193–1214.
  • Cediel-Ulloa A., Lupu D.I., Johansson Y,. Hinojosa M., Özel F., Rüegg J. (2022) Impact of endocrine disrupting chemicals on neurodevelopment: the need for better testing strategies for endocrine disruption-induced developmental neurotoxicity. Expert Review of Endocrinology & Metabolism; 17, 131–141.

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