Neuroinflammation and Neuropil Pathology in Schizophrenia and Bipolar Disorder: A Post-mortem Study

This project is sponsored by the Stanley Medical Research Institute:

The proposed research will investigate possible indicators of neuroinflammation and neuropil pathology in schizophrenia and bipolar disorder. Indications of an immune (co)etiology come from the findings of dysregulated cytokine networks, the association of schizophrenia with certain HLA haplotypes and viral / toxoplasmic infections. Moreover, the typical long-term course of schizophrenia and bipolar disorder with onset in early adulthood, progressive as well as benign courses, exacerbations and remissions, shows similarities to various autoimmune disorders (e.g., multiple sclerosis, psoriasis, myasthenia gravis) and leads to the speculation of similar pathogenetic components. In addition to a well established neurodevelopmental component in the pathogenesis of schizophrenia, several MRI-studies reported a subtle progressive loss of brain tissue, while the majority of post mortem studies could not show a loss of nerve cells. This subtle progressive reduction of cortical tissue volume loss without loss of neurons suggests that changes may occur in the connecting elements between neurons, i.e. in the neuropil and /or glial cells, and this may be progressive over time. Interestingly, several studies revealed increased levels of S100B in peripheral blood and CSF of patients with schizophrenia. Elevated concentrations of this protein, which is formed in astrocytes and oligodendrocytes, led to a rarification of dendrites and synapses in animal experiments. Thus one could speculate on a causal link between elevated S100B levels and the above mentioned alterations of neuropil in schizophrenia.

Using whole-brain serial sections from the New Magdeburg Brain Collection, proteins or peptides assumed to be markers for inflamatory/autoimmnological processes or for different types of glia cells will be investigated quantitatively by immunohistochemistry in brains from schizophrenics, bipolar patients and normal controls. Several brain regions will be examined which are assumed to play a particular role in the pathophysiology of schizophrenia an bipolar disorder: anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex, superior temporal cortex, hippocampus, mediodorsal thalamic nucleus and hypothalamus.

Part 1: Search for neuroinflammatory processes

Part 2: Analysis for disturbances in myelination / neuropil pathology / axonal damage