Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia
Open accessAbstract
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.
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CSPGs are involved in the pathophysiology of schizophrenia.
“Emerging evidence from human postmortem, animal model and genetic studies points to their involvement in the pathophysiology of schizophrenia (SZ).1, 2, 3, 4, 5, 6, 7”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [1]
Human post-mortem studies show disease-specific reduction in PNN density and altered expression of genes regulating PNNs/ECM in amygdala, olfactory epithelium, entorhinal cortex, superior temporal cortex, and prefrontal cortex in schizophrenia.
“a number of human post-mortem brain studies have revealed a disease-specific reduction in the density of PNNs as well as altered expression of genes that regulate PNNs and ECM in key brain structures associated with schizophrenia, including the amygdala, olfactory epithelium, entorhinal cortex, superior temporal cortex and prefrontal cortex”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Pantazopoulos et al., 2013
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Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity
Frischknecht, R., Heine, M., Perrais, D., Seidenbecher, C. I., Choquet, D., & Gundelfinger, E. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2338 · Cited by 554 · cited 1× · see citing works
“Mailstop 149, 115 Mill Street, 1 617 855 2040. retta). ghts reserved. differentiation and migration, maturation of synapses and regulation of neurotransmitter receptor availability (Meyer-Puttlitz et al., 1996; Frischknecht et al., 2009; Maeda et al., 2010).”
BackgroundNeural regeneration and the peripheral olfactory system
Schwob, J. E. (2002) · The Anatomical Record · doi:10.1002/ar.10047 · Cited by 506 · cited 3× · see citing works
“…diagnosed with schizophrenia Harry Pantazopoulos a,b, Anne Boyer-Boiteau b, Eric H. Holbrook c,d, Woochan Jang d, Chang-Gyu Hahn e, Steven E. Arnold e, Sabina Berretta a,b,f,⁎ a Department of Psychiatry, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA b Translational…”
BackgroundOlfactory marker protein during ontogeny: Immunohistochemical localization
Farbman, A. I., & Margolis, F. L. (1980) · Developmental Biology · doi:10.1016/0012-1606(80)90062-7 · Cited by 400 · cited 2× · see citing works
“J), a marker for mature ORNs (Farbman and Margolis, 1980; Hahn et al., 2005), while 15.0% of p-CSPG + ORNs were found to be OMP-positive.”
BackgroundInfluentialOlfactory Dysfunction in Schizophrenia A Qualitative and Quantitative Review
Moberg, P. J. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00019-6 · Cited by 317 · cited 3× · see citing works
“Scatter plots show themean (black line) and 95% confidence intervals peripheral sensory structures, potentially contributing to functional sensory impairment (Moberg et al., 1999; Turetsky et al., 2009).”
BackgroundVerhaagen, J., Oestreicher, A. B., Gispen, W. H., & Margolis, F. L. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-02-00683.1989 · Cited by 309 · cited 2× · see citing works
“1E–G), a protein prevalently contained in immature ORNs (Verhaagen et al., 1989; Hahn et al., 2005), while only 1.”
BackgroundInfluentialPantazopoulos, H., Woo, T.-U. W., Lim, M. P., Lange, N., & Berretta, S. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.196 · Cited by 296 · cited 2× · see citing works
“In particular, CSPG-enriched perineuronal nets were decreased in several brain regions, often in associationwithmarked increased of CSPG-positive glial cells (Pantazopoulos et al., 2010; Enwright et al., 2012; Mauney et al., 2013).”
BackgroundSelf-citationChondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS?
Rhodes, K. E., & Fawcett, J. W. (2003) · Journal of Anatomy · doi:10.1111/j.1469-7580.2004.00261.x · Cited by 296 · cited 1× · see citing works
“We suggest that this transition may involve a shift in the ORN interactions with other cells and the extracellular environment (Rhodes and Fawcett, 2004; Carulli et al., 2005; Dityatev et al., 2010).”
BackgroundCell dynamics in the olfactory mucosa
Graziadei, P. P. C. (1973) · Tissue and Cell · doi:10.1016/s0040-8166(73)80010-2 · Cited by 294 · cited 4× · see citing works
“…McLean Hospital, 115 Mill St., Belmont, MA 02478, USA c Dept. of Otology and Laryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA d Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison…”
BackgroundInfluentialMauney, S. A., Athanas, K. M., Pantazopoulos, H., Shaskan, N., Passeri, E., Berretta, S., & Woo, T.-U. W. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.007 · Cited by 291 · cited 2× · see citing works
“In particular, CSPG-enriched perineuronal nets were decreased in several brain regions, often in associationwithmarked increased of CSPG-positive glial cells (Pantazopoulos et al., 2010; Enwright et al., 2012; Mauney et al., 2013).”
BackgroundSelf-citationMorphology of the human olfactory epithelium
Morrison, E. E., & Costanzo, R. M. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.902970102 · Cited by 277 · cited 2× · see citing works
“Morphologically distinct CSPG+ cell categories were identified in the OE (see Moran et al., 1982; Morrison and Costanzo, 1990; Holbrook et al., 2011).”
BackgroundMethodIdentification and molecular regulation of neural stem cells in the olfactory epithelium
Beites, C. L., Kawauchi, S., Crocker, C. E., & Calof, A. L. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.03.027 · Cited by 265 · cited 2× · see citing works
“During the course of their maturation, newly formed ORN axons join odorspecific axon bundles to reach the corresponding olfactory bulb glomeruli (Graziadei, 1973; Yoshihara and Mori, 1997; Beites et al., 2005).”
Background[Chondroitin sulfate proteoglycans in neural development and regeneration].
Gu, W.-L., & Lu, P. (2007) · PubMed · Cited by 255 · see citing works
Dours-Zimmermann, M. T., & Zimmermann, D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)30089-2 · Cited by 249 · see citing works
Olfaction: A potential cognitive marker of psychiatric disorders
Atanasova, B., Graux, J., El‐Hage, W., Hommet, C., Camus, V., & Belzung, C. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.05.003 · Cited by 236 · cited 1× · see citing works
“This phenomenon may contribute robust olfactory deficits detected in subjects with SZ (Kopala et al., 1993; Moberg et al., 1999; Brewer et al., 2001; Atanasova et al., 2008).”
BackgroundDityatev, A. E., Seidenbecher, C. I., & Schachner, M. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.08.003 · Cited by 229 · cited 1× · see citing works
“We suggest that this transition may involve a shift in the ORN interactions with other cells and the extracellular environment (Rhodes and Fawcett, 2004; Carulli et al., 2005; Dityatev et al., 2010).”
BackgroundHayar, A. M., Karnup, S. V., Shipley, M. T., & Ennis, M. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4714-03.2004 · Cited by 219 · cited 2× · see citing works
“…the lamina propria and through the lamina cribrosa, and eventually forming bundles segregated by odor specificity and reaching odor specific glomeruli in the olfactory bulb (Gonzalez and Silver, 1994; Yoshihara and Mori, 1997; Tisay and Key, 1999; Belluscio and Katz, 2001; Hayar et al., 2004).”
BackgroundSymmetry, Stereotypy, and Topography of Odorant Representations in Mouse Olfactory Bulbs
Belluscio, L., & Katz, L. C. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-06-02113.2001 · Cited by 216 · cited 2× · see citing works
“…the lamina propria and through the lamina cribrosa, and eventually forming bundles segregated by odor specificity and reaching odor specific glomeruli in the olfactory bulb (Gonzalez and Silver, 1994; Yoshihara and Mori, 1997; Tisay and Key, 1999; Belluscio and Katz, 2001; Hayar et al., 2004).”
BackgroundChondroitin sulfate proteoglycans in neural development and regeneration
Laabs, T. L., Carulli, D., Geller, H. M., & Fawcett, J. W. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.01.014 · Cited by 211 · cited 1× · see citing works
“We suggest that this transition may involve a shift in the ORN interactions with other cells and the extracellular environment (Rhodes and Fawcett, 2004; Carulli et al., 2005; Dityatev et al., 2010).”
BackgroundImmunohistochemical characterization of human olfactory tissue
Holbrook, E. H., Wu, E., Curry, W. T., Lin, D. T., & Schwob, J. E. (2011) · The Laryngoscope · doi:10.1002/lary.21856 · Cited by 189 · cited 4× · see citing works
“Total numbers of cells were not calculated because the anatomical characteristics of the OE, which is constituted of islands intermingled with RE (Holbrook et al., 2011), do not allow reliable total volume estimates.”
BackgroundMethodInfluentialSelf-citationExtracellular matrix abnormalities in schizophrenia
Berretta, S. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.010 · Cited by 179 · cited 1× · see citing works
“Together, these abnormalities have been postulated to disrupt neurodevelopmental processes, including neuronal migration, circuit formation and consolidation (Berretta, 2012).”
BackgroundSelf-citationBrewer, W. J., Pantelis, C., Anderson, V. A., Velakoulis, D., SINGH, B. S., Copolov, D., & McGorry, P. D. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.1.107 · Cited by 140 · cited 1× · see citing works
“This phenomenon may contribute robust olfactory deficits detected in subjects with SZ (Kopala et al., 1993; Moberg et al., 1999; Brewer et al., 2001; Atanasova et al., 2008).”
BackgroundMcCurdy, R. D., Feron, F. P., Perry, C., Chant, D. C., McLean, D. E., Matigian, N., Hayward, N. K., McGrath, J. J., & Mackay‐Sim, A. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2005.10.012 · Cited by 138 · cited 3× · see citing works
“Notably, disturbances of OE cell cycle include lower density of basal cells and increase of postmitotic immature ORNs, providing strong support for a dysregulation of OE neuronal lineage (Feron et al., 1999; Arnold et al., 2001; Perry et al., 2002; McCurdy et al., 2006).”
BackgroundThe expression and functions of glycoconjugates in neural stem cells
Yanagisawa, M., & Yu, R. K. (2007) · Glycobiology · doi:10.1093/glycob/cwm018 · Cited by 135 · cited 1× · see citing works
“CSPG role in regulating brain cell differentiation (Yanagisawa and Yu, 2007; Purushothaman et al., 2012) suggests that theymay contribute toOEbasal cell differentiation and theirmaturation into ORNs.”
BackgroundOlfactory deficits in neuroleptic naive patients with schizophrenia
Kopala, L. C., Clark, C. C., & Hurwitz, T. A. (1993) · Schizophrenia Research · doi:10.1016/0920-9964(93)90022-b · Cited by 133 · cited 1× · see citing works
“This phenomenon may contribute robust olfactory deficits detected in subjects with SZ (Kopala et al., 1993; Moberg et al., 1999; Brewer et al., 2001; Atanasova et al., 2008).”
BackgroundIn vivo and in vitro neurogenesis in human olfactory epithelium
Hahn, C.-G., Han, L., Rawson, N. E., Mirza, N. A., Borgmann‐Winter, K. E., Lenox, R. H., & Arnold, S. E. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20424 · Cited by 129 · cited 4× · see citing works
“1E–G), a protein prevalently contained in immature ORNs (Verhaagen et al., 1989; Hahn et al., 2005), while only 1.”
BackgroundInfluentialSelf-citationDysregulation of Olfactory Receptor Neuron Lineage in Schizophrenia
Arnold, S. E., Han, L., Moberg, P. J., Turetsky, B. I., Gur, R. E., Trojanowski, J. Q., & Hahn, C.-G. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.9.829 · Cited by 125 · cited 12× · see citing works
“…while the discrepancy between c-CSPG-ORNs decreases in this study and normal density of OMP + ORNs previously reported in the same subject cohort (Arnold et al., 2001) indicates reduced CSPG expression in these neurons, results from the 2001 study do not allow to unambiguously interpret…”
BackgroundMethodResultInfluentialSelf-citationvon Holst, A., Sirko, S., & Faissner, A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0422-06.2006 · Cited by 124 · cited 2× · see citing works
“The observed pericellular pattern of CSPG labeling (WFA and phosphacan) in basal cells is highly reminiscent of that of CSPG expression in neural stem/cell progenitors (NSCPs) in stem cell niches of the embryonic and adult brain (Ito et al., 2005; von Holst et al., 2006).”
BackgroundThe Extracellular Matrix Modulates Olfactory Neurite Outgrowth on Ensheathing Cells
Tisay, K. T., & Key, B. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-22-09890.1999 · Cited by 122 · cited 2× · see citing works
“…the lamina propria and through the lamina cribrosa, and eventually forming bundles segregated by odor specificity and reaching odor specific glomeruli in the olfactory bulb (Gonzalez and Silver, 1994; Yoshihara and Mori, 1997; Tisay and Key, 1999; Belluscio and Katz, 2001; Hayar et al., 2004).”
BackgroundSirko, S., von Holst, A., Weber, A., Wizenmann, A., Theocharidis, U., Götz, M., & Faissner, A. (2010) · Stem Cells · doi:10.1002/stem.309 · Cited by 119 · cited 2× · see citing works
“As mentioned above, cell surface CSPG expression in NSCPs is needed for cell differentiation and maturation, mediated by interactions with growth factors (Sirko et al., 2010).”
BackgroundAltered adhesion, proliferation and death in neural cultures from adults with schizophrenia
Feron, F. P., Perry, C., Hirning, M. H., McGrath, J. J., & Mackay‐Sim, A. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00055-9 · Cited by 117 · cited 3× · see citing works
“…olfactory epithelium; OMP, olfactory mar ceptor neuron; PBS–Tx, phosphate buffer–Triton X; p-CSP fate proteoglycan; PMI, postmortem time interval; RE, receptor tyrosine phosphatase zeta; SCID, Structured Disorders; SZ, schizophrenia; WFA,Wisteria floribunda ag ⁎ Corresponding author at: MRC3…”
BackgroundIto, Y., Hikino, M., Yajima, Y., Mikami, T., Sirko, S., von Holst, A., Faissner, A., Fukui, S., & Sugahara, K. (2004) · Glycobiology · doi:10.1093/glycob/cwi036 · Cited by 114 · cited 1× · see citing works
“The observed pericellular pattern of CSPG labeling (WFA and phosphacan) in basal cells is highly reminiscent of that of CSPG expression in neural stem/cell progenitors (NSCPs) in stem cell niches of the embryonic and adult brain (Ito et al., 2005; von Holst et al., 2006).”
BackgroundVersican V1 Isoform Induces Neuronal Differentiation and Promotes Neurite Outgrowth
Wu, Y., Sheng, W., Chen, L., Dong, H., Lee, V., Lu, F., Wong, C. S., Lu, W.-Y., & Yang, B. B. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0667 · Cited by 107 · cited 1× · see citing works
“CSPGs, and versican in particular, promote axon outgrowth (Wu et al., 2004; Maeda, 2010; Klausmeyer et al., 2011).”
BackgroundPurushothaman, A., Sugahara, K., & Faissner, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.298430 · Cited by 102 · cited 3× · see citing works
“…3400 Spruce Street, Philadelphia, PA 19104, USA f Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA Abbreviations: BSA, bovine albumin serum; CPZ, chlor cytoplasmic chondroitin sulfate proteoglycan; CSPG, ch GAG, glycosaminoglycan; GAP43, growth…”
BackgroundBuxbaum, J. D., Georgieva, L., Young, J. J., Plescia, C., Kajiwara, Y., Jiang, Y., Moskvina, V, Norton, N., Peirce, T., Williams, H., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4001991 · Cited by 86 · cited 3× · see citing works
“CSPG functions, including regulation of neuronal differentiation and migration, are highly relevant to the pathophysiology of SZ.”
BackgroundAltered Cell Cycle Dynamics in Schizophrenia
Fan, Y., Abrahamsen, G., McGrath, J. J., & Mackay‐Sim, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.004 · Cited by 75 · cited 2× · see citing works
“…mar ceptor neuron; PBS–Tx, phosphate buffer–Triton X; p-CSP fate proteoglycan; PMI, postmortem time interval; RE, receptor tyrosine phosphatase zeta; SCID, Structured Disorders; SZ, schizophrenia; WFA,Wisteria floribunda ag ⁎ Corresponding author at: MRC3 McLean Hospital — Belmont, MA 02478, USA.”
BackgroundAxon-glia interactions regulate ECM patterning in the postnatal rat olfactory bulb
Gonzalez, M., & Silver, J. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-10-06121.1994 · Cited by 63 · cited 4× · see citing works
“…the lamina propria and through the lamina cribrosa, and eventually forming bundles segregated by odor specificity and reaching odor specific glomeruli in the olfactory bulb (Gonzalez and Silver, 1994; Yoshihara and Mori, 1997; Tisay and Key, 1999; Belluscio and Katz, 2001; Hayar et al., 2004).”
BackgroundInfluentialAfferent connections of the dorsal premammillary nucleus
Comoli, E., Ribeiro-Barbosa, �. R., & Canteras, N. S. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000717)423:1 · Cited by 61 · see citing works
Olfactory Receptor Neuron Dysfunction in Schizophrenia
Turetsky, B. I., Hahn, C.-G., Arnold, S. E., & Moberg, P. J. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.139 · Cited by 59 · cited 1× · see citing works
“1E–G), a protein prevalently contained in immature ORNs (Verhaagen et al., 1989; Hahn et al., 2005), while only 1.9% of c-CSPG + ORN was GAP43-positive.”
BackgroundInfluentialSelf-citationLocalization of aggrecan and versican in the developing rat central nervous system.
Popp, S., Andersen, J. S., Maurel, P., & Margolis, R. U. (2003) · Developmental Dynamics · doi:10.1002/dvdy.10282 · Cited by 55 · cited 2× · see citing works
“CSPG functions, including regulation of neuronal differentiation and migration, are highly relevant to the pathophysiology of SZ.”
BackgroundTakahashi, N., Sakurai, T., Bozdagi-Gunal, O., Dorr, N. P., Moy, J., Krug, L., Gama-Sosa, M. A., Elder, G. A., Koch, R. J., Walker, R. H., et al. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.8 · Cited by 48 · see citing works
Chondroitin sulfate proteoglycans in neural development and plasticity
Maeda, N. (2010) · Frontiers in Bioscience · doi:10.2741/3637 · Cited by 44 · cited 2× · see citing works
“differentiation and migration, maturation of synapses and regulation of neurotransmitter receptor availability (Meyer-Puttlitz et al., 1996; Frischknecht et al., 2009; Maeda et al., 2010).”
BackgroundOlfactory physiological impairment in first-degree relatives of schizophrenia patients
Turetsky, B. I., Köhler, C., Gur, R. C., & Moberg, P. J. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.03.013 · Cited by 44 · cited 1× · see citing works
“Given the role that CSPGs play in cell differentiation and ORN neurite outgrowth and axon guidance, altered CSPG expression may contribute to cell lineage and olfactory identification abnormalities detected in SZ (Arnold et al., 2001; Turetsky et al., 2008).”
BackgroundStructural Variation of Chondroitin Sulfate and Its Roles in the Central Nervous System
Maeda, N. (2010) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152410790780136 · Cited by 43 · cited 1× · see citing works
“CSPGs, and versican in particular, promote axon outgrowth (Wu et al., 2004; Maeda, 2010; Klausmeyer et al., 2011).”
BackgroundBasic principles and molecular mechanisms of olfactory axon pathfinding
Yoshihara, Y., & Mori, K. (1997) · Cell and Tissue Research · doi:10.1007/s004410050953 · Cited by 41 · cited 3× · see citing works
“During the course of their maturation, newly formed ORN axons join odorspecific axon bundles to reach the corresponding olfactory bulb glomeruli (Graziadei, 1973; Yoshihara and Mori, 1997; Beites et al., 2005).”
BackgroundThalamic afferents to the motor cortex in the cat. A horseradish peroxidase study
Morán, A., Avendaño, C., & Reinoso‐Suárez, F. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90376-7 · Cited by 41 · cited 3× · see citing works
“Morphologically distinct CSPG+ cell categories were identified in the OE (see Moran et al., 1982; Morrison and Costanzo, 1990; Holbrook et al., 2011).”
BackgroundMethodArnold, S. E., & Rioux, L. (2001) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a006883 · Cited by 35 · cited 3× · see citing works
“: +1 617 855 3484; fax: + E-mail address: s.berretta@mclean.harvard.edu (S. Ber 0920-9964/$ – see front matter © 2013 Elsevier B.V.”
BackgroundSelf-citationOlfactory Neural Cells: An Untapped Diagnostic and Therapeutic Resource
Perry, C. F., Mackay‐Sim, A., Feron, F. P., & McGrath, J. J. (2002) · The Laryngoscope · doi:10.1097/00005537-200204000-00002 · Cited by 30 · see citing works
Klausmeyer, A., Conrad, R., Faissner, A., & Wiese, S. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22531 · Cited by 24 · cited 1× · see citing works
“CSPGs, and versican in particular, promote axon outgrowth (Wu et al., 2004; Maeda, 2010; Klausmeyer et al., 2011).”
BackgroundSchizophrenia susceptibility genes and their neurodevelopmental implications: focus on neuregulin 1.
Harrison, P. J. (2007) · PubMed · Cited by 17 · see citing works
Schizophrenia Susceptibility Genes and their Neurodevelopmental Implications: Focus on Neuregulin 1
Harrison, P. J. (2008) · Novartis Foundation symposium · doi:10.1002/9780470994030.ch17 · Cited by 15 · cited 1× · see citing works
“These functions bear direct relevance to the pathophysiology of schizophrenia (SZ), a disease with a strong neurodevelopmental component (e.g. Arnold and Rioux, 2001; Harrison, 2007).”
BackgroundMeyer-Puttlitz (1996) · doi:10.1002/(sici)1096-9861(19960226)366:1
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Self-citationCórdova-Palomera, A., Fatjó-Vilas, M., Gastó, C., Navarro, V, Krebs, M.-O., & Fañanás, L. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.49 · Cited by 117 · see citing works
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“In parallel to PNN-related findings, these changes did not appear to depend on altered cell numbers and did not depend on disease-related confounding factors such as exposure to pharmacological treatment, substance abuse, onset and duration of the illness, and so forth, further supporting the idea that altered CSPG ex…”
BackgroundSelf-citationPerineuronal nets and schizophrenia: The importance of neuronal coatings
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.018 · Cited by 95 · see citing works
Translational potential of olfactory mucosa for the study of neuropsychiatric illness
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Self-citationPaylor, J. W., Lins, B. R., Greba, Q., Moen, N., de Moraes, R. S., Howland, J. G., & Winship, I. R. (2016) · Scientific Reports · doi:10.1038/srep37580 · Cited by 80 · see citing works
The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia
Chelini, G., Pantazopoulos, H., Durning, P. T., & Berretta, S. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.02.003 · Cited by 73 · see citing works
“Human postmortem studies from our group consistently show marked decreases of PNNs in people with SZ [136,138,158–160].”
BackgroundSelf-citationAberrant glycosylation in schizophrenia: a review of 25 years of post-mortem brain studies
Williams, S., Mealer, R. G., Scolnick, E. M., Smoller, J. W., & Cummings, R. D. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0761-1 · Cited by 73 · see citing works
Neural ECM in addiction, schizophrenia, and mood disorder
Lubbers, B. R., Smit, A. B., Spijker, S., & van den Oever, M. C. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00012-8 · Cited by 60 · see citing works
Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research
Lavoie, J., Sawa, A., & Ishizuka, K. (2017) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000327 · Cited by 57 · see citing works
Klein, J., Le, M., & Zaia, J. (2018) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000766 · Cited by 57 · see citing works
“Lectins are also used for staining tissue proteoglycans but leave the underlying proteoglycan structure undefined (21-23).”
BackgroundProteomics, Glycomics, and Glycoproteomics of Matrisome Molecules
Raghunathan, R., Sethi, M. K., Klein, J., & Zaia, J. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r119.001543 · Cited by 53 · see citing works
Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study
Kiparizoska, S., & Ikuta, T. (2017) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx045 · Cited by 53 · see citing works
“A reduced quantity of chondroitin sulfate proteoglycans is found in the olfactory epithelium tissues of patients of schizophrenia (Pantazopoulos et al., 2013), which may be accounted for by the pathology of olfactory dysfunction in schizophrenia.”
BackgroundPerineuronal Nets: Subtle Structures with Large Implications
Carceller, H., Gramuntell, Y., Klimczak, P., & Nácher, J. (2022) · The Neuroscientist · doi:10.1177/10738584221106346 · Cited by 48 · see citing works
Office‐based olfactory mucosa biopsies
Holbrook, E. H., Rebeiz, L., & Schwob, J. E. (2016) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21711 · Cited by 43 · see citing works
Self-citationGlycosaminoglycans and Glycomimetics in the Central Nervous System
Rowlands, D., Sugahara, K., & Kwok, J. C. F. (2015) · Molecules · doi:10.3390/molecules20033527 · Cited by 43 · see citing works
Olfactory Dysfunction in Autoimmune Central Nervous System Neuroinflammation
Kim, J., Choi, Y., Ahn, M., Jung, K., & Shin, T. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1001-4 · Cited by 41 · see citing works
Bitanihirwe, B. K. Y., Mauney, S. A., & Woo, T.-U. W. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.03.1047 · Cited by 37 · see citing works
Byun, J., Son, S. M., Cha, M.-Y., Shong, M., Hwang, Y. J., Kim, Y. S., Ryu, H., Moon, M., Kim, K.-S., & Mook‐Jung, I. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.184 · Cited by 31 · see citing works
Serial in-solution digestion protocol for mass spectrometry-based glycomics and proteomics analysis
Sethi, M. K., Downs, M. J., & Zaia, J. (2020) · Molecular Omics · doi:10.1039/d0mo00019a · Cited by 31 · see citing works
Mueller, T., Yates, S. D., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.10.024 · Cited by 31 · see citing works
“…glycosylation pathways (Bauer et al., 2010; Berretta, 2012; Berretta et al., 2015; Ikemoto, 2014; Mueller et al., 2014; Narayan et al., 2009; Pantazopoulos et al., 2013; Stanta et al., 2010; Telford et al., 2012; Tucholski et al., 2013b, 2013a) and dysregulated expression of glycosylation…”
BackgroundInfluentialThe Role of Perineuronal Nets in Physiology and Disease: Insights from Recent Studies
Auer, S., Schicht, M., Hoffmann, L., Budday, S., Frischknecht, R., Blümcke, I., & Paulsen, F. P. (2025) · Cells · doi:10.3390/cells14050321 · Cited by 30 · see citing works
“Moreover, post-mortem studies of the olfactory epithelium revealed differences in the expression of CSPGs [140].”
Klimczak, P., Rizzo, A., Castillo-Gómez, E., Pérez-Rando, M., Gramuntell, Y., Beltrán, M. A. C. S., & Nácher, J. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.733989 · Cited by 29 · see citing works
Matrisome changes in Parkinson’s disease
Downs, M. J., Sethi, M. K., Raghunathan, R., Layne, M. D., & Zaia, J. (2022) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-022-03929-4 · Cited by 28 · see citing works
“Established mass spectrometry-based proteomics methods often do not describe matrisome protein glycosylation due to low sequence coverage and a large number of possible proteoforms [18].”
BackgroundBenítez‐King, G., Valdés‐Tovar, M., Trueta, C., Galván‐Arrieta, T., Argueta, J., Alarcón-Elizalde, S., Lora-Castellanos, A., & Solís‐Chagoyán, H. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.01.013 · Cited by 28 · see citing works
Melrose, J. (2019) · Advanced Biosystems · doi:10.1002/adbi.201800327 · Cited by 26 · see citing works
Mass spectrometry methods for analysis of extracellular matrix components in neurological diseases
Downs, M. J., Zaia, J., & Sethi, M. K. (2022) · Mass Spectrometry Reviews · doi:10.1002/mas.21792 · Cited by 23 · see citing works
Gottschling, C., Geißler, M., Springer, G., Wolf, R. J., Juckel, G., & Faissner, A. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.08.055 · Cited by 22 · see citing works
Tee, J. Y., Sutharsan, R., Fan, Y., & Mackay‐Sim, A. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.03.005 · Cited by 19 · see citing works
“Additionally, chondroitin sulfate proteoglycan expression is reduced in post - mortem patient olfactory epithelium (Pantazopoulos et al., 2013).”
Wu, X., Shukla, R., Alganem, K., Zhang, X., Eby, H., Devine, E. A., DePasquale, E. A. K., Reigle, J. K., Simmons, M. S., Hahn, M., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01205-y · Cited by 20 · see citing works
Self-citationLi, S.-T., Young, T., & Huang, T. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120738 · Cited by 14 · see citing works
Wegrzyn, D., Manitz, M. P., Kostka, M., Freund, N., Juckel, G., & Faissner, A. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14934 · Cited by 14 · see citing works
Yang, K., Hua, J., Etyemez, S., Paez, A. G., Prasad, N., Ishizuka, K., Sawa, A., & Kamath, V. J. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2021.07.016 · Cited by 14 · see citing works
Huang, T., Li, S.-T., Wang, Y., & Young, T. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.08.022 · Cited by 12 · see citing works
Filho, A. J. M. C., Mottin, M., Lós, D. B., Andrade, C. H., & Macêdo, D. S. (2022) · Biochimie · doi:10.1016/j.biochi.2022.07.015 · Cited by 11 · see citing works
Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
Yuan, X., Wang, Y., Ali, M. A., Qin, Z., Guo, Z., Zhang, Y., Zhang, M., Zhou, G., Yang, J., Chen, L., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021664 · Cited by 10 · see citing works
“The alteration in the expression of GAGs contributes to olfactory receptor neuron (ORN) dysregulation and abnormal olfactory molecules identification in the pathophysiology of schizophrenia [38].”
BackgroundMueller, T., Simmons, M. S., Helix, A. T., Haroutunian, V. H., & Meador‐Woodruff, J. H. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/369314 · Cited by 7 · see citing works
“…protein trafficking and subcellular targeting and has been shown in multiple studies to be abnormal in schizophrenia (Berretta, 2012; Ikemoto, 2014; Mueller et al., 2014; Narayan et al., 2009; Pantazopoulos et al., 2013; Sato and Kitajima, 2013; Stanta et al., 2010; Tucholski et al., 2013b, 2013a).”
BackgroundRole of Neurotransmitters in the Functioning of Olfactory Sensory Neurons
Bigdai, E. V., & Samoilov, V. O. (2022) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093022030206 · Cited by 6 · see citing works
Brown, J. S. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105206 · Cited by 6 · see citing works
Meyer, A., Truman, K. A., Totlani, J., William, C., Brown, H., Shah, S. R., Hirsch, D., Salem, M., Chang, T., Abdelsalam, R., et al. (2024) · The International Journal of Psychiatry in Medicine · doi:10.1177/00912174241310091 · Cited by 5 · see citing works
RetractedComplex Impairments to the Olfactory Sensory System in Schizophrenia
Bigdai, E. V., Samoilov, V. O., & Sinegubov, A. A. (2022) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-022-01280-w · Cited by 5 · see citing works
Regulation of CNS Plasticity Through the Extracellular Matrix
Warren, P. M., Dickens, S., Gigout, S., Fawcett, J. W., & Kwok, J. C. F. (2018) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190635374.013.11 · Cited by 5 · see citing works
Sánchez-Florentino, Z. A., Romero-Martínez, B. S., Flores‐Soto, E., Serrano, H., Montaño, L., Valdés‐Tovar, M., Calixto, E., Aquino‐Gálvez, A., López-Riquelme, G. O., Alvarado, R., et al. (2023) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2023.5331 · Cited by 2 · see citing works
Blockus, H., & Chédotal, A. (2015) · Wiley eBooks · doi:10.1002/9781118524947.ch8 · Cited by 2 · see citing works
DNA methylation signatures associated with early-onset schizophrenia in Chinese patients
Zhan, N., Leung, P. B. M., Zhong, Y., Wong, K. C. Y., Hui, T. C. K., So, H.-C., Sham, P. C., Wong, C. C. Y., & Lui, S. S. Y. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03869-y · Cited by 1 · see citing works
Extracellular Matrix Abnormalities in Major Psychoses: CS-6 Expression in Human Dermal Fibroblasts
Ronxhi, J. (2017) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
- Authors
- Pantazopoulos, H., Boyer-Boiteau, A., Holbrook, E. H., Jang, W., Hahn, C.-G., Arnold, S. E., & Berretta, S.
- Affiliations
- Harvard University (US)
- Tufts University (US)
- University of Pennsylvania (US)
- Corresponding author
- Berretta, Sabina
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 150
- Issue
- 2-3
- Pages
- 366-372
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC4215560
- OpenAlex
- W2020188570
- Cited by
- 47
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 3
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH091348, R01MH086522, R01MH059852)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- schizophrenia, chondroitin sulfate proteoglycans
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biopsy, Female, Humans, Male, Middle Aged, Olfactory Mucosa, Proteoglycans, Receptors, Cell Surface, Schizophrenia, Case-Control Studies, GAP-43 Protein, Receptors, N-Acetylglucosamine, Plant Lectins, Olfactory Marker Protein, Versicans, Receptor-Like Protein Tyrosine Phosphatases, Class 5
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