title: Increased levels of GAP-43 protein in schizophrenic brain tissues demonstrated by a novel immunodetection method.
abstract: Studies on the molecular basis of neurological and psychiatric disorders often rely on the precise determination of specific proteins in brain tissues. In this study, we have developed a method for measuring the levels of the neural-specific growth-associated protein, GAP-43, in human postmortem brain specimens. This rapid and quantitative method is based on immunodetection procedures. Briefly, synaptosomal plasma membranes (SPMs) are deposited onto polyvinylidene difluoride (PVDF) membranes via a dot-blotting apparatus, followed by specific GAP-43 detection using a monospecific polyclonal antibody. Overall, the dot-blot procedure provided several advantages over Western blots and one-dimensional and two-dimensional polyacrylamide gels. The assays were more sensitive, reproducible, and allowed the rapid and simultaneous determination of multiple samples. Using this technique, we examined the levels of the GAP-43 protein in Brodmann's areas 17, 20, and 10 of schizophrenic and age-, sex-, and postmortem interval (PMI) matched controls. These studies revealed an increase in the levels of GAP-43 in visual association and frontal cortices (areas 20 and 10) of schizophrenic brains. Given the relationship of GAP-43 expression with the establishment and remodeling of neural connections, our results support the hypothesis that schizophrenia is associated with a perturbed organization of synaptic connections in associative areas of the human brain.
authors.affiliation: Department of Chemistry, University of New Mexico School of Medicine, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Sower
authors.forename: E D
authors.initials: ED
authors.lastname: Bird
authors.forename: N I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D019922:GAP-43 Protein; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism; D016900:Neurofilament Proteins / Q000032:analysis; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D013574:Synaptosomes / Q000737:chemistry / Q000473:pathology; D014793:Visual Cortex / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
chemical_list: D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D006220:Haloperidol