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

Abstract

Schizophrenia is a serious mental disease in which patients are showing a wide array of symptoms as well as several brain abnormalities. Both genetic and environmental factors have been implicated in the etiology of schizophrenia. According to the neurodevelopmental hypothesis, several disrupting events during brain development may be responsible for the onset of the disease. The implication of inflammatory processes during pregnancy contributing to the risk of developing schizophrenia has lead to the development of rodent animal models using the so called maternal immune activation. The rodent LPS model induces maternal immune responses by the injection of bacterial lipopolysaccharides, resulting in offspring showing a variety of neuropathological, behavioral 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). However, investigations of functional connectivity in animal models of schizophrenia are lacking. Therefore, the aim of this study was to investigate restingstate functional connectivity in the rat LPS model of schizophrenia on a longitudinal scale from the juvenile stage (PD~30), over puberty (PD~45) and late adolescence (PD~66) until adulthood (PD~94). Independent component analysis (ICA) revealed seven resting-state networks including the so called default mode network, somatosensory and motor networks, a a striatal network as well as a cerebellar network. Effects of age on connectivity in the cerebellar network and somatosensory networks unrelated to the treatment could be observed, but no effects of LPS treatment on connectivity of the identified restingstate networks could be shown. However, as the results from complementary behavioral experiments for the assessment of schizophrenia-like symptoms in the animals hint towards methodological problems in the implementation of the LPS model, further investigations exploring the functional connectivity of rats with a more refined implementation of the LPS model should be carried out in order to complement the results of this study.