Andreas Coors (PhD-student)

Resting-state brain connectivity in the rat LPS model of schizophrenia

Schizophrenia is a serious mental disease, that is believed to result from several disrupting ‘hits’ during neurodevelopment, leading to altered developmental processes and finally to the onset of the disease. Several genetic and environmental factors have been implicated in its etiology. The implication of inflammatory processes during pregnancy contributing to the risk of developing schizophrenia has led to the development of rodent animal models using the so called maternal immune activation. The rodent LPS (lipopolysaccharide) model induces maternal immune responses by the injection of bacterial lipopolysaccharides, resulting in offspring showing a variety of neuropathological, behavioural and pharmacological abnormalities, similar to schizophrenic patients.

Several studies have reported an altered functional connectivity of schizophrenic patients, as measured by resting-state functional magnetic resonance imaging (fMRI). This technique offers to be a useful translational tool for investigation of the causes of the disease as well as for the development of new treatment strategies. Since investigations of functional connectivity in animal models of schizophrenia are lacking, the aim of this PhD project is to investigate the functional connectivity in offspring of LPS treated rats on a longitudinal scale. Resting-state fMRI measurements are complemented by contemporary behavioural experiments for the assessment of schizophrenia-like deficits, including the elevated plus maze (EPM) task, the novel object recognition (NOR) task, as well as prepulse inhibition (PPI) of the acoustic startle reflex. Furthermore, the involvement of microglia in the formation of LPS induced abnormalities is examined using immunohistochemical studies