title: Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia.
abstract: Emerging evidence points to proteoglycan abnormalities in the pathophysiology of schizophrenia (SZ). In particular, markedly abnormal expression of chondroitin sulfate proteoglycans (CSPGs), key components of the extracellular matrix, was observed in the medial temporal lobe. CSPG functions, including regulation of neuronal differentiation and migration, are highly relevant to the pathophysiology of SZ. CSPGs may exert similar functions in the olfactory epithelium (OE), a continuously regenerating neural tissue that shows cell and molecular abnormalities in SZ. We tested the hypothesis that CSPG expression in OE may be altered in SZ. CSPG-positive cells in postmortem OE from non-psychiatric control (n=9) and SZ (n=10) subjects were counted using computer-assisted light microscopy. 'Cytoplasmic' CSPG (c-CSPG) labeling was detected in sustentacular cells and some olfactory receptor neurons (c-CSPG+ORNs), while 'pericellular' CSPG (p-CSPG) labeling was found in basal cells and some ORNs (p-CSPG+ORNs). Dual labeling for CSPG and markers for mature and immature ORNs suggests that c-CSPG+ORNs correspond to mature ORNs, and p-CSPG+ORNs to immature ORNs. Previous studies in the same cohort demonstrated that densities of mature ORNs were unaltered (Arnold et al., 2001). In the present study, numerical densities of c-CSPG+ORNs were significantly decreased in SZ (p<0.025; 99.32% decrease), suggesting a reduction of CSPG expression in mature ORNs. Previous studies showed a striking increase in the ratios of immature neurons with respect to basal cells. In this study, we find that the ratio of p-CSPG+ORNs/CSPG+basal cells was significantly increased (p=0.03) in SZ, while numerical density changes of p-CSPG+ORNs (110.71% increase) or CSPG+basal cells (53.71% decrease), did not reach statistical significance. Together, these results indicate that CSPG abnormalities are present in the OE of SZ and specifically point to a reduction of CSPG expression in mature ORNs in SZ. Given the role CSPGs play in OE cell differentiation and axon guidance, we suggest that altered CSPG expression may contribute to ORN lineage dysregulation, and olfactory identification abnormalities, observed in SZ.
authors.affiliation: Department of Psychiatry, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Translational Neuroscience Laboratory, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Pantazopoulos
authors.forename: Anne
authors.initials: A
authors.lastname: Boyer-Boiteau
authors.forename: Eric H
authors.initials: EH
authors.lastname: Holbrook
authors.forename: Woochan
authors.initials: W
authors.lastname: Jang
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Hahn
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Sabina
authors.initials: S
authors.lastname: Berretta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D051842:Olfactory Marker Protein / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism*; D037121:Plant Lectins; D011509:Proteoglycans / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D034781:Receptors, N-Acetylglucosamine; D012559:Schizophrenia / Q000473:pathology*; D053675:Versicans / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D051842:Olfactory Marker Protein; D037121:Plant Lectins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D034781:Receptors, N-Acetylglucosamine; C487486:chondroitin sulfate proteoglycan receptor, human; C040129:wisteria lectin; D053675:Versicans; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: BSA; CPZ; CSPG; Chondroitin sulfate proteoglycans; Extracellular matrix; GAG; GAP43; NSCP; OE; OMP; ORN; Olfactory epithelium; PBS–Tx; PMI; Postmortem; RE; RPTPz; SCID; SZ; Schizophrenia; Structured Clinical Interview for DSM Disorders; WFA; Wisteria floribunda agglutinin; bovine albumin serum; c-CSPG; chlorpromazine-equivalent; chondroitin sulfate proteoglycan; cytoplasmic chondroitin sulfate proteoglycan; glycosaminoglycan; growth associate protein 43; neural stem/cell progenitor; olfactory epithelium; olfactory marker protein; olfactory receptor neuron; p-CSPG; pericellular chondroitin sulfate proteoglycan; phosphate buffer–Triton X; postmortem time interval; receptor tyrosine phosphatase zeta; respiratory epithelium; schizophrenia
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