Growth-associated protein 43 (GAP-43) and synaptophysin alterations in the dentate gyrus of patients with schizophrenia.
Growth-associated protein 43 (GAP-43) expression is critical for the proper establishment of neural circuitry, a process thought to be disrupted in schizophrenia. Previous work from our laboratory demonstrated decreased GAP-43 levels in post-mortem tissue from the entire hippocampal formation of affected individuals. In the present study, we used immunocytochemical techniques to localize alterations in GAP-43 protein to specific synapses. GAP-43 distribution was compared to that of synaptophysin, another synaptic protein known to be altered in schizophrenia. The levels and distribution of GAP-43 and synaptophysin proteins were measured in the dentate gyrus of subjects with schizophrenia and sex-, age-, and postmortem interval-matched normal controls and subjects with bipolar disorder. Tissue from subjects was provided by the Harvard Brain Tissue Resource Center. In control subjects, GAP-43 immunostaining was prominent in synaptic terminals in the inner molecular layer and hilar region. Subjects with schizophrenia had significant decreases in GAP-43 immunoreactivity in the hilus (p<0.05, paired t-test) and inner molecular layer (p<0.05, paired t-test) but not in the outer molecular layer. In the same tissues, synaptophysin immunoreactivity was significantly reduced in both the inner and outer molecular layers of the dentate gyrus (both p<0.01 by paired t-test), but not in the hilus. In contrast to patients with schizophrenia, GAP-43 and synaptophysin levels in subjects with bipolar disorder did not differ from controls. Given the relationship of GAP-43 and synaptophysin with the development and plasticity of synaptic connections, the observed alterations in the hippocampus of patients with schizophrenia may be related to cognitive deficits associated with this illness.
Chambers
Jessie S
JS
Department of Neurosciences, University of New Mexico School of Medicine, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
Thomas
Deirdre
D
Saland
Linda
L
Neve
Rachael L
RL
Perrone-Bizzozero
Nora I
NI
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000378:metabolism; D016022:Case-Control Studies; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D012559:Schizophrenia / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism*
D019922:GAP-43 Protein; D016708:Synaptophysin