Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex

The expression of telencephalic reelin (Reln) and glutamic acid decarboxyla se mRNAs and their respective cognate proteins is down-regulated in postmor tem brains of schizophrenia and bipolar disorder patients. To interpret the pathophysiological significance of this finding, immunoelectron microscopi c experiments are required, but these cannot be carried out in postmortem h uman brains. As an alternative, we carried out such experiments in the cort ex of rats and nonhuman primates. We found that Rein is expressed predomina ntly in layer I of both cortices and is localized to bitufted (double-bouqu et), horizontal, and multipolar gamma-aminobutyric acid-ergic interneurons, which secrete Rein into extracellular matrix, Rein secretion is mediated b y a constitutive mechanism that depends on the expression of a specific sig nal peptide present in the Rein carboxy-terminal domain. Extracellular matr ix Rein is found to aggregate in proximity of postsynaptic densities expres sed in apical dendrite spines, which include also the alpha(3) subunit of i ntegrin receptors, Most pyramidal neurons of various cortical layers expres s the mouse-disabled 1 (Dab1) protein, which, after phosphorylation by a so luble tyrosine kinase, functions as an adapter protein, probably mediating a modulation of cytoskeleton protein expression. We hypothesize that the de crease of neuropil and dendritic spine density reported to exist in the neo cortex of psychiatric patients may be related to a down-regulation of Rein- integrin interactions and the consequent decrease of cytoskeleton protein t urnover.