The growth-associated protein GAP-43 is increased in the hippocampus and in the gyrus cinguli in schizophrenia.
Schizophrenia is a common and severe psychiatric disorder of unknown etiology. Numerous neuropathological studies have found subtle structural changes in limbic structures, especially medial temporal lobe structures and the gyrus cinguli. To test the hypothesis that synaptic disturbances are involved in the pathogenesis of schizophrenia, we studied the growth-associated protein 43 (GAP-43), a protein localized to presynaptic terminals, suggested to be involved in establishment and remodeling of synaptic connections, in postmortem brain tissue, using quantitative Western blotting immunohistochemistry. The material consisted of brain tissue from 17 schizophrenics (80 +/- 11 yr), diagnosed according to the DSM-III-R criteria, and 20 age-matched controls (75 +/- 13 yr). Quantitative analyses showed increased GAP-43 protein levels in schizophrenic compared to control brains, both in the hippocampus (2.43 +/- 0.78 vs 1.00 +/- 0.29; p < 0.0001) and in the gyrus cinguli (1.52 +/- 0.21 vs 1.00 +/- 0.35; p < 0.0001). Also by immunohistochemistry, increased GAP-43 staining was found in schizophrenic compared with control brains, throughout all layers of the gyrus cinguli and the hippocampus. Anomalous synaptic sprouting and reorganization, with resultant "miswiring," as well as a defect in synaptic pruning have been hypothesized to be pathogenetic factors in schizophrenia. We suggest that a decreased synaptic density, whether caused by disturbed development or damage/degeneration, may elicit a reactive synaptogenesis (reflected by an increase in GAP-43), which may be functional or anomalous. Synaptic pathology in the limbic system may be of importance in the development of psychotic symptoms in schizophrenia.
Blennow
K
K
Göteborg University, Institute of Clinical Neuroscience, Department of Psychiatry and Neurochemistry, Sahlgren's University Hospital, Mölndal, Sweden.
Bogdanovic
N
N
Gottfries
C G
CG
Davidsson
P
P
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D012559:Schizophrenia / Q000378:metabolism*
D019922:GAP-43 Protein