Stress during the neonatal period can create mental health problems later in life. In the Early Life Stress (ELS) research line, we focus on the (lasting) impact of ELS on physiology, behavior, immunology, brain function and metabolism. In our ELS mouse model, employing the limited bedding and nesting (LBN) paradigm, we aim to mimic environmental stress as may be experienced by neonates at the Neonatal Intensive Care Unit (NICU. This research line helps to bridge the gap between clinical reality and preclinical research. In order to do that we are in regular contact with colleagues at the department of Neonatology. In the future we want to determine how neonatal stress may reprogram the brain, leading to immunological and functional impairments in later life, with the aim to develop tailor-made treatment strategies.

Overview

In our research we not only focus on the brain, but also take into account crosstalk with peripheral organs including spleen, liver, bone marrow and blood. The Early Life Stress (ELS) research line currently focuses on three types of projects;

1. Crosstalk periphery-brain,
2. Immune effects of ELS and
3. The impact of paternal care to modulate the effects of ELS.

1. Crosstalk periphery-brain

We are investigating specific fluorescent tracers (e.g. fluorescein) to determine blood-brain barrier integrity after ELS. Importantly, we assess potential BBB leakage in specific brain regions. In follow-up experiments we explore the connection between the behavioral impairments seen in stressed mice seen and the brain regions involved. We are now also investigating important proteins for BBB function, such as claudin-5.

Image: Brain tissue of a mouse pup at postnatal day 9 showing claudin-5 protein expression, a critical marker for BBB integrity. Courtesy of Merle Nijenhuis.

2. Inflammation Project

Early life adversity in humans has been connected to long-term inflammation. In our mouse model we mimic this phenomenon; mice exposed to ELS display evidence for immune activation in the body (see e.g. below an image from the spleen in stressed [LBN] mice). Immune changes are also seen in other bodily tissues of stressed mice. We believe that immunological changes are centrally linked to the long-term negative consequences of ELS.

Image: Splenic tissue from mice at postnatal day 9. (a) Enlarged lymphocyte clusters are detected in stressed (LBN) mouse pups, as compared to controls. (b) In addition, the clusters are also more segregated in stressed mouse pups. Courtesy of Cindy Cleypool.

3. Sharing is Caring: Paternal Care Project

The neonatal period can be highly stressful, for the infant, as well as for the parents. High levels of stress are particularly prominent in prematurely born infants, necessarily exposed to the environmental stressors of the neonatal intensive care unit (NICU). An important factor modulating parental stress is social support. Partner support, in the form of aid and attachment, has been linked to lower emotional distress postpartum and less distressed infants. In this project we investigate whether and how paternal care in mice can block negative consequences of ELS. The closely monitor the parental care provided by both the mouse parents, we employ automated animal tracking.

Video: Automated tracking made possible by analyzing videos via DeepLabCut. Courtesy of Ella Sommer.