Research Lieselotte Van Bockstal

Abstract

Intrauterine growth restriction (IUGR) describes a pathological condition in which the fetus fails to grow to its biological potential, primarily because of poor placental function. IUGR affects 8% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. IUGR can cause neurological deficiencies, however the mechanisms underlying these deficiencies remain to be determined. With the wide range of neurodevelopmental disorders associated with IUGR, the use of animal models appropriate to investigating mechanisms of injury in the IUGR newborn is crucial for the development of effective and targeted therapies for babies. The perinatal development of the central nervous system in pigs is very similar to that in humans. Piglets are therefore considered a solid model to explore how perinatal insults affect brain structure and function. This project aims to look for proteins in the hippocampus with important roles in the neuronal development and function where sex differences in IUGR have been described earlier in order to explain the better adaptation of female IUGR piglets compared to male piglets. The importance to map the morphological differences in the hippocampus can help us to understand the pathophysiology of neurodevelopmental disorders later in life. This is important because new insights into the pathophysiology can lead to novel therapeutic or preventive therapies against IUGR.

Researcher(s)

• Promoter: Van Bockstal Lieselotte

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The central objective of this project is to demonstrate that early-life stress is a risk factor for the development of gastrointestinal dysfunction and that males and females differ in how they cope with early-life stress. This differing response is believed to be present already in utero, whereby it is suggested that the male offspring is disadvantaged in responding to stressors during pregnancy. However, during postnatal development, the female appears to be the weaker sex when it comes to the development of a leaky gut and a dysfunctional gastrointestinal tract. In this project, we want the study sex-related differences in intestinal permeability during the period when the gastrointestinal tract undergoes extensive developmental changes. During this window of plasticity, stressors can disrupt the normal developmental process, having long-lasting effects on the gut. Therefore, we will include early life stress during late gestation (intrauterine growth restriction) or during the juvenile phase (chronic stress during artificial rearing) in our set-up to research whether males and females mount a differing response. This will be done in a newborn and juvenile piglet.

Researcher(s)

• Promoter: Van Ginneken Chris
• Co-promoter: Van Bockstal Lieselotte
• Fellow: Banous Naya
• Fellow: Mohaghegh Toosi Ali

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are able to survive inside macrophages. Miltefosine is an oral drug used to treat VL patients but is increasingly failing to permanently clear parasites from the patient. Parasites from these relapse patients do not seem to display an increased resistance to the drug but are able to modify the immune system to promote survival inside macrophages even in conditions where the drug is administered. The impact of drug treatment on parasite survival will be evaluated in various tissues using molecular and imaging technologies in rodent models of VL following a natural parasite transmission. Combination of this information with the quantification of drug levels in these tissues, will allow to pinpoint in which tissues parasites are most likely to survive drug treatment. The expression of genes following infection and drug treatment will be analyzed inside infected liver macrophages (Kupffer cells, KCs) in order to understand how parasites from relapsed patients can survive inside host cells. Using transgenic mouse models, this research will allow to evaluate the impact of KCs and KC gene expression on infection and treatment outcome. Collectively, the proposed multidisciplinary approach will improve our understanding of the complex interactions between the parasite, its host and the drug and will allow the formulation of recommendations for improved treatment interventions.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Van Bockstal Lieselotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are able to survive inside macrophages. Miltefosine is an oral drug used to treat VL patients but is increasingly failing to permanently clear parasites from the patient. Parasites from these relapse patients do not seem to display an increased resistance to the drug but are able to modify the immune system to promote survival inside macrophages even in conditions where the drug is administered. The impact of drug treatment on parasite survival will be evaluated in various tissues using molecular and imaging technologies in rodent models of VL following a natural parasite transmission. Combination of this information with the quantification of drug levels in these tissues, will allow to pinpoint in which tissues parasites are most likely to survive drug treatment. The expression of genes following infection and drug treatment will be analyzed inside infected liver macrophages (Kupffer cells, KCs) in order to understand how parasites from relapsed patients can survive inside host cells. Using transgenic mouse models, this research will allow to evaluate the impact of KCs and KC gene expression on infection and treatment outcome. Collectively, the proposed multidisciplinary approach will improve our understanding of the complex interactions between the parasite, its host and the drug and will allow the formulation of recommendations for improved treatment interventions.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Van Bockstal Lieselotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project