Reduction of chromogranin B-like immunoreactivity in distinct subregions of the hippocampus from individuals with schizophrenia

Synaptic disturbances may play a key role in the pathophysiology of schizophrenia. This study was designed to further investigate possible synaptic alterations in the brains of chronic schizophrenic patients. Chromogranin B was applied as a marker for large dense core vesicles and synapsin I as a protein associated with the synaptic vesicle membrane. The distribution and density of chromogranin B-and synapsin I-like immunoreactivity in subregions of the hippocampus was compared between controls (n = 16) and patients with schizophrenia (n = 17). The overall distribution of hippocampal chromogranin B- and synapsin I-like immunoreactivity was similar in controls and in schizophrenic patients with the highest densities in the terminal field of mossy fibers and in the inner molecular layer of the dentate gyrus. In schizophrenic hippocampi, a significant reduction in the density of chromogranin B-like immunoreactivity was found in the CA4 and CA3 but not in the CA1 area of the dentate gyrus based on computerized image analysis. The loss of immunoreactivity was localized to mossy fibers and terminals surrounding hilar interneurons. Double-labelling immunohistochemistry revealed that synapsin I was co-expressed with chromogranin B in these neuronal structures and was also significantly reduced in schizophrenic hippocampi. The present study demonstrates an area-specific reduction of chromogranin B which is paralleled by a decrease of synapsin I. The loss of presynaptic proteins involved in distinct steps of exocytosis may cause complex synaptic disturbances in specific hippocampal subregions resulting in an imbalanced neurotransmitter availability in schizophrenic patients.