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.