The main objective of Dr. Duque-Wilckens’ research is to identify novel neuro-immune mechanisms that underlie emotional regulation. These findings may help to create new therapeutic tools for the prevention and/or treatment of depression and anxiety, the two most prevalent mood disorders affecting society today.
Dr. Duque-Wilckens received her doctorate in veterinary medicine from the University of Chile. Here, she developed a deep interest in understanding the bidirectional link between emotional well-being and peripheral disease, which motivated her to continue her education at University of California, Davis. At UC Davis, Natalia joined Brian Trainor’s lab, where she primarily focused on understanding how oxytocin can increase anxiety in certain contexts. Her graduate work, published in Neuropharmacology1, Biological Psychiatry2,3, and PNAS4, collectively showed for the first time that a distinct, stress-sensitive oxytocin circuit within the bed nucleus of the stria terminalis acts to drive an anxiety-related phenotype in potentially dangerous social contexts, providing key insights into the mechanisms explaining why oxytocin can enhance the salience of both, positive and negative social interactions. During her time at the Trainor lab, Dr. Duque-Wilckens was also awarded an AALAS grant to investigate the effects of different housing systems on California mice behavior. This work, published in Applied Animal Behavior Science5, showed that increasing social and environmental complexity reduces in-cage stereotypic backflipping behavior while reducing the variability (and therefore increasing experimental power) of stress-induced behavioral phenotypes in this species.
Natalia then joined the labs of Dr. Robison and Dr. Moeser at Michigan State University to spearhead a project studying the role of mast cells -innate immune cells mostly known for their role in peripheral inflammation- in mood regulation. To pursue this project, Dr. Duque-Wilckens was awarded a NARSAD Young Investigator Grant in 2019, from which two main lines of research emerged. Her first project, published in Brain, Behavior and Immunity6, showed that exposure to early life adversity increases adult sensitivity to develop depressive-like behavior and exacerbates the meningeal inflammatory response to adult stress. Importantly, both effects of early life stress are prevented by pharmacological inhibition of mast cells, suggesting that these cells could play an important role connecting early life adversity and adult psychopathology. In her second project, Dr. Duque-Wilckens used a combination of genetic models together with in vitro and in vivo studies to show that inhibition of FosB, a transcription factor known to play pivotal roles in neuronal function, increases mast cell mediator release as well as systemic inflammation and clinical symptomatology in response to allergens and pathogens (manuscript in progress)7. For this work, Dr. Duque-Wilckens was awarded the American Association of Immunology Trainee Award in 2021.
Based on the evidence that mast cells have the capacity to affect neuronal and glial function and are ubiquitous in the developing and adult brain across vertebrate species, in her independent lab Dr. Duque-Wilckens will use sophisticated behavioral tools, cell culture, pharmacology, microscopy, and single cell studies to expand our understanding of the nature of brain mast cells and their role on brain development and behavior. This goal is supported by some very intriguing findings that stem from the development of novel tools that allowed Dr. Duque-Wilckens to study brain mast cells in ways that were previously not possible. Among other things, these findings demonstrated that brain mast cells adopt distinct phenotypes, and that they play a role in modulating neural circuits involved in anxiety behaviors.
1. Duque-Wilckens, N. et al. Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects. Neuropharmacology 110, 59–68 (2016).
2.Duque-Wilckens, N. et al. Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress-Induced Social Avoidance in Female California Mice. Biol. Psychiatry 83, 203–213 (2018).
3.Steinman, M. Q. et al. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin. Biological Psychiatry 80, 406–414 (2016).
4.Duque-Wilckens, N. et al. Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance. PNAS 117, 26406–26413 (2020).
5.Minie, V. A. et al. Enriched laboratory housing increases sensitivity to social stress in female California mice (Peromyscus californicus). Applied Animal Behaviour Science 241, 105381 (2021).
6.Duque-Wilckens, N. et al. Early life Adversity Drives Sex-Specific Anhedonia and Meningeal Immune Gene Expression Through Mast Cell Activation. Brain, Behavior, and Immunity (2022)
7.Duque-Wilckens, N. et al. Mast cell-specific inactivation of Fosb exacerbates release of pro-inflammatory mediators in models of systemic anaphylaxis and lipopolysaccharide-induced sepsis. The Journal of Immunology 206, 97.12-97.12 (2021).
8.Gao, Y. et al. Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors. Commun Biol 4, 1–10 (2021).