The dual hit hypothesis of schizophrenia.

stress inflammation schizophrenia

dr. E.F.J. de Vries
dr. J. Doorduin
C. Guerrin

Nature of the research:
Animal studies, stress, PET imaging, molecular research, cellular research

Fields of study:
cell biology molecular imaging nuclear medicine

Background / introduction
Exposure to chronic stress or traumatic events is known to increase the risk of developing mood or anxiety disorders. The negative impact of traumatic events appears to be worse if they occur during brain development in prenatal or juvenile age than in adulthood. These stressors are believed to prime and alter the immune system. The primed immune system would react differently to immune challenges later in life, therefore increasing the risk for developing mood disorders and mood-related symptoms such as social withdrawal and anhedonia.
Animal studies allow for the identification of a direct link between stress, inflammation, and behavior. Hence, we would like to study the effect of traumatic events during juvenile age and adulthood and their consequences later in life when exposed to an immune challenge. To do so, we will use repeated social defeat and endotoxin injection. We aim to determine whether social defeat during adolescence, primes the immune system to be more responsive to an immune challenge/infection later in life.
Research question / problem definition
1. To investigate to what extent prenatal microglia priming or exposure to adolescent stressors alone induce schizophrenic-like behaviour.
2. To investigate if a combination of prenatal microglia priming and adolescent stressors have a synergistic effect.
3. To investigate if the behavioural effects are accompanied by neuroinflammation and changes in the dopaminergic system.
Rats will be exposed to either no stressor or social defeat during juvenile age or young adulthood, and then injected with an endotoxin later in life. Doing this will allow us to determine the priming effect of social defeat on peripheral and brain inflammation. The project aims to determine the effect of social defeat on peripheral and brain inflammation, and behavior, as well as the interaction between them.

Repeated positron emission tomography (PET) scans will be used to measure neuroinflammation in the brain. The rats will undergo simple and short-lasting behavioral experiments to determine possible behavioral alterations. The brain and tissue of the rats will be collected for further postmortem analysis.
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