Animal Models Based on Immune Challenge: The Link to Brain Changes and Schizophrenia

Abstract

Within the pathophysiology of schizophrenia, microglial cells seem to play the most important role. Early changes within the embryonal phase and neurodegenerative processes lead to activation of microglia cells, which-via the neurotoxic activities of these cells-induces a rarification of synaptic connections in frontal and temporal brain regions, i.e. reduction of the neuropil. Promising inflammational models in rodents for schizophrenia with high validity can be today used to mimic behavioral as well as neurobiological findings in patients, e.g. the well-known neurochemical alterations within the dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. The microglial activation can also be well modelled within one of these models, i.e. the inflammational PolyI:C animal model of schizophrenia, having a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then trigger neurodegeneration, must be now investigated further on in broad detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia especially concerning the interaction of immune activation, inflammation, and neurodegeneration. Furthermore, this should lead to the development of better treatment options and of preventive interventions.