Brevican-containing perineuronal nets of extracellular matrix in dissociated hippocampal primary cultures
Abstract
Perineuronal nets (PNN) are specialized extracellular matrix structures enwrapping CNS neurons, which are important regulators for neuronal and synaptic functions. Brevican, a chondroitin sulfate proteoglycan, is an integral component of PNN. Here, we have investigated the appearance of these structures in hippocampal primary cultures. The expression profile of brevican in mixed cultures resembles the in vivo pattern with a strong upregulation of all isoforms during the second and 3rd weeks in culture. Brevican is primarily synthesized by co-cultured glial fibrillary acidic protein (GFAP-)-positive astrocytes and co-assembles with its interaction partners in PNN-like structures on neuronal somata and neurites as identified by counterstaining with the PNN marker Vicia villosa lectin. Both excitatory and inhibitory synapses are embedded into PNN. Furthermore, axon initial segments are strongly covered by a dense brevican coat. Altogether, we show that mature primary cultures can form PNN, and that basic features of these extracellular matrix structures may be studied in vitro.
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The ECM in the AIS seems to be mainly comprised of brevican.
“However, the ECM seems to be mainly comprised of brevican (John et al., 2006).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as John et al., 2006
Brevican enrichment in the AIS is mediated via direct interaction with NF186, which is diminished by knockdown of NF186.
“Brevican enrichment in the AIS was mediated via direct interaction with NF186, which was diminished by a knockdown of NF186 (John et al., 2006;Hedstrom et al., 2007).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as John et al., 2006
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Self-citationOrganization and maintenance of molecular domains in myelinated axons
Buttermore, E. D., Thaxton, C., & Bhat, M. A. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23197 · Cited by 92 · see citing works
Hayani, H., Song, I., & Dityatev, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00149 · Cited by 84 · see citing works
The crosstalk of hyaluronan-based extracellular matrix and synapses
Frischknecht, R., & Seidenbecher, C. I. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09990226 · Cited by 84 · see citing works
Self-citationThe protein tyrosine phosphatase RPTPζ/phosphacan is critical for perineuronal net structure
Eill, G. J., Sinha, A., Morawski, M., Viapiano, M. S., & Matthews, R. T. (2020) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)49907-8 · Cited by 32 · see citing works
Strackeljan, L., Baczynska, E., Cangalaya, C., Baidoe-Ansah, D., Wlodarczyk, J., Kaushik, R., & Dityatev, A. (2021) · Cells · doi:10.3390/cells10081862 · Cited by 71 · see citing works
“The following primary reagents were used: chicken anti-PV (1:500, Synaptic Systems, Göttingen, Germany, 195006), biotinylated Wisteria floribunda agglutinin (WFA, 1:1000, Vector laboratories B-1355, Burlingame, CA, USA), rabbit anti-Bcan [32,33] (1:1000), guinea pig anti-vGluT1 (1:1500, Synaptic Systems, 135304), mous…”
MethodThe Axon Initial Segment, 50 Years Later
Leterrier, C. (2015) · Current topics in membranes · doi:10.1016/bs.ctm.2015.10.005 · Cited by 79 · see citing works
Diverse functions of perineuronal nets
Karetko, M., & Skangiel-Kramska, J. (2009) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2009-1766 · Cited by 76 · see citing works
“These results indicate that tenascin-R is essential for ECM proteoglycans to form the lattice-like structure (Weber et al. 1999, Haunso et al. 2000).”
BackgroundInfluentialMentlein, R., Hattermann, K., Hemion, C., Jungbluth, A. A., & Held‐Feindt, J. (2010) · Biological Chemistry · doi:10.1515/bc.2010.119 · Cited by 76 · see citing works
“Brevican exists in two splice variants, the dominant secreted form with a 97 kDa core protein and approximately 100 kDa of attached chondroitin sulfate, and a glycosylphosphatidylinositol-anchored, truncated form; both are primarily synthesized by astroglial cells (Gary et al., 2000; John et al., 2006).”
BackgroundMatrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons
de Wit, J., Toonen, R. F. G., & Verhage, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3931-08.2009 · Cited by 73 · see citing works
“In these cases release was strictly synaptic and the extracellular presence may therefore be attributable to interactions with the ECM, which is concentrated at synapses (John et al., 2006).”
BackgroundLiu, X., Ying, J., Wang, X., Zheng, Q., Zhao, T., Yoon, S., Yu, W., Yang, D., Yang, F., & Hua, F. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.729273 · Cited by 70 · see citing works
Buttermore, E. D., Piochon, C., Wallace, M. L., Philpot, B. D., Hansel, C., & Bhat, M. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5602-11.2012 · Cited by 68 · see citing works
“, 2010), and rabbit anti-Brevican (John et al., 2006).”
BackgroundIntrinsic and extrinsic determinants of ion channel localization in neurons
Hedstrom, K. L., & Rasband, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04001.x · Cited by 67 · see citing works
“Finally, two recent reports showed that there is an enrichment of the extracellular matrix (ECM) molecules aggrecan and brevican around the AIS (Bruckner et al. 2006; John et al. 2006).”
BackgroundHamel, M. G., Ajmo, J. M., Leonardo, C. C., Zuo, F., Sandy, J. D., & Gottschall, P. E. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.11.014 · Cited by 60 · see citing works
“The glial scar is an accumulation of reactive astrocytes and extracellular matrix (ECM) molecules such as chondroitin sulfate (CS)-substituted PGs, tenascin and other proteins that inhibit the re-growth of axons and the migration of certain cells into the damaged region (Davies, et al., 1999, Davies, et al., 1997, Lay…”
MethodInfluentialBlosa, M., Sonntag, M., Brückner, G., Jäger, C., Seeger, G., Matthews, R. T., Rübsamen, R., Arendt, T., & Morawski, M. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.10.003 · Cited by 59 · see citing works
Composition, assembly, and maintenance of excitable membrane domains in myelinated axons
Rasband, M. N. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.09.010 · Cited by 59 · see citing works
“The chondroitin sulfate proteoglycans brevican and versican are both found at the AIS and CNS nodes of Ranvier [47-49].”
BackgroundMimicking the Brain Extracellular Matrix in Vitro: A Review of Current Methodologies and Challenges
Rauti, R., Renous, N., & Maoz, B. M. (2019) · Israel Journal of Chemistry · doi:10.1002/ijch.201900052 · Cited by 57 · see citing works
Nakamura, M., Nakano, K., Morita, S., Nakashima, T., Oohira, A., & Miyata, S. (2009) · Brain Research · doi:10.1016/j.brainres.2008.11.022 · Cited by 54 · see citing works
“CSPGs consist of a core protein and sulfated glycosaminoglycans (GAGs) (Bandtlow and Zimmermann, 2000; Yamaguchi, 2000) and are generally known to inhibit neurite outgrowth (Oohira et al., 1991; Katoh-Senba et al., 1995).”
Neural ECM molecules in axonal and synaptic homeostatic plasticity
Frischknecht, R., Chang, K.-J., Rasband, M. N., & Seidenbecher, C. I. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00004-9 · Cited by 53 · see citing works
Self-citationLettau, I. D., Hattermann, K., Held‐Feindt, J., Brauer, R., Sedlacek, R., & Mentlein, R. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181ce9f67 · Cited by 52 · see citing works
“Brevican exists in 2 splice variants, the dominant secreted form with a 97-kd core protein and approximately 60 kd of attached chondroitin sulfate, and a glycosylphosphatidylinositol-anchored truncated form; both are primarily synthesized by astroglial cells (41).”
BackgroundHyaluronan-based extracellular matrix under conditions of homeostatic plasticity
Valenzuela, J. C., Heise, C., Franken, G., Singh, J. B., Schweitzer, B., Seidenbecher, C. I., & Frischknecht, R. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0606 · Cited by 46 · see citing works
Self-citationHyaluronan synthesis by developing cortical neurons in vitro
Fowke, T. M., Karunasinghe, R. N., Bai, J.-Z., Jordan, S., Gunn, A. J., & Dean, J. M. (2017) · Scientific Reports · doi:10.1038/srep44135 · Cited by 47 · see citing works
“In the present study, we found no obvious overlap of hyaluronan with synaptophysin or PSD-95, which is supported by evidence that perineuronal net components enclose synapses, but are absent from the sites of synaptic contact 46,58 .”
InfluentialMitlöhner, J., Kaushik, R., Niekisch, H., Blondiaux, A., Gee, C. E., Happel, M. F. K., Gundelfinger, E., Dityatev, A., Frischknecht, R., & Seidenbecher, C. (2020) · Cells · doi:10.3390/cells9020260 · Cited by 47 · see citing works
“As previously reported by us and others, at this time-point, the cultures had reliably developed a HAbased ECM with similar composition as in vivo [17,18,20].”
Self-citationThe Synaptic Extracellular Matrix: Long-Lived, Stable, and Still Remarkably Dynamic
Dankovich, T. M., & Rizzoli, S. O. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.854956 · Cited by 44 · see citing works
Excitable Domains of Myelinated Nerves
Chang, K.-J., & Rasband, M. N. (2013) · Current topics in membranes · doi:10.1016/b978-0-12-417027-8.00005-2 · Cited by 42 · see citing works
Extracellular matrixes and neuroinflammation
Jang, D. G., Sim, H. J., Song, E. K., Kwon, T., & Park, T. J. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.10.156 · Cited by 42 · see citing works
“It is expressed by neurons, astrocytes, and oligodendrocytes (25-27).”
BackgroundHeikkinen, A., Pihlajaniemi, T., Faissner, A., & Yuzaki, M. (2014) · Progress in Brain Research · doi:10.1016/b978-0-444-63486-3.00002-5 · Cited by 42 · see citing works
Ajmo, J. M., Bailey, L. A., Howell, M. D., Cortez, L. K., Pennypacker, K. R., Mehta, H. N., Morgan, D., Gordon, M. N., & Gottschall, P. E. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06647.x · Cited by 41 · see citing works
“Brevican-containing, dense network of ECM in the nervous system, wraps around synapses where irregularly deposited proteins bind to anchored membrane ‘receptors’ to form surface compartments around the synapse (John et al. 2006; Frischknecht et al. 2009).”
Enzymatic Degradation of Cortical Perineuronal Nets Reverses GABAergic Interneuron Maturation
Willis, A., Pratt, J. A., & MORRIS, B. J. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02772-z · Cited by 35 · see citing works
“1c), a CSPG which is prevalent throughout the mature PNN structure but is thought to be enriched around the axonal initial segment [64, 65], after ChABC treatment.”
BackgroundDifferential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex
Virgintino, D., Perissinotto, D., Girolamo, F., Mucignat, M. T., Montanini, L., Errede, M., Kaneiwa, T., Yamada, S., Sugahara, K., Roncali, L., et al. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00694.x · Cited by 36 · see citing works
“All members of the lectican family have been shown to be synthetic products of cultured multipotent neural progenitor cells [12, 27], capable of reproducing PNN-like structures [28], and aggrecan seems to be specifically involved in neural cell–cell aggregation phenomena [29–30].”
BackgroundPantazopoulos, H., Murray, E. A., & Berretta, S. (2008) · Brain Research · doi:10.1016/j.brainres.2008.02.036 · Cited by 34 · see citing works
Expression profiling of human glial precursors
Campanelli, J. T., Sandrock, R. W., Wheatley, W., Xue, H., Zheng, J., Liang, F., Chesnut, J. D., Zhan, M., Rao, M. S., & Liu, Y. M. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-102 · Cited by 34 · see citing works
“Brevican is a neural-specific chondroitin sulfate proteoglycan and is expressed in mature astrocytes and downregulated in adult rat spinal cords [50,51].”
Su, J., Cole, J., & Fox, M. A. (2017) · ASN NEURO · doi:10.1177/1759091416689020 · Cited by 33 · see citing works
Rushton, E., Rohrbough, J. C., & Broadie, K. S. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21864 · Cited by 34 · see citing works
The protein tyrosine phosphatase RPTPζ/phosphacan is critical for perineuronal net structure
Eill, G. J., Sinha, A., Morawski, M., Viapiano, M. S., & Matthews, R. T. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010830 · Cited by 32 · see citing works
Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats
Wakao, N., Imagama, S., Zhang, H., Tauchi, R., Muramoto, A., Natori, T., Takeshita, S., Ishiguro, N., Matsuyama, Y., & Kadomatsu, K. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.11.051 · Cited by 31 · see citing works
The emerging role of the chondroitin sulfate proteoglycan family in neurodegenerative diseases
Lin, J., Duan, M.-R., Lin, N., & Zhao, W. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0146 · Cited by 29 · see citing works
Ueno, H., Suemitsu, S., Murakami, S., Kitamura, N., Wani, K., Matsumoto, Y., Okamoto, M., & Ishihara, T. (2018) · IBRO Reports · doi:10.1016/j.ibror.2018.11.006 · Cited by 26 · see citing works
“Brevican has been shown to be significantly involved in nerve excitability in the axon initial segment (John et al., 2006).”
BackgroundShabani, Z., Ghadiri, T., Karimipour, M., Sadigh‐Eteghad, S., Mahmoudi, J., Mehrad, H., & Farhoudi, M. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.01.006 · Cited by 28 · see citing works
Blondiaux, A., Jia, S., Annamneedi, A., Çalışkan, G., Nebel, J., Montenegro‐Venegas, C., Wykes, R. C., Fejtová, A., Walker, M. C., Stork, O., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106324 · Cited by 26 · see citing works
“…1:1000 for Western blots [WB] and 1:500 for immunohistochemistry [IHC]) and rabbit anti-Brevican (1:1000 for WB) (Seidenbecher et al., 1995; John et al., 2006); rabbit anti-Aggrecan (Millipore, AB1031, 1:500 for WB; RRID:AB_90460); sheep anti-Neurocan (R & D Systems, AF5800; 1:200 for WB;…”
Self-citationKlausmeyer, A., Conrad, R., Faissner, A., & Wiese, S. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22531 · Cited by 24 · see citing works
“…isoforms of phosphacan/RPTPb (rabbit polyclonal 1:50; Klausmeyer et al., 2007); pAb NC-2 antineurocan (rabbit polyclonal 1:200; Retzler et al., 1996); pAb antibrevican (guinea pig polyclonal 1:200; John et al., 2006); and pAb KAF14 anti-tenascin-C (rabbit polyclonal 1:200; Faissner et al., 1990).”
BackgroundA Composite Sketch of Fast-Spiking Parvalbumin-Positive Neurons
Bartholomé, O., Bonardeaux, O. D. L. B., Neirinckx, V., & Rogister, B. (2020) · Cerebral Cortex Communications · doi:10.1093/texcom/tgaa026 · Cited by 21 · see citing works
“In cortical and hippocampal PV+ neurons, it has been shown that the majority of AMPARs lacks the GluA2 subunit, making it permeable to Ca2+ (Jonas et al. 1994; Geiger et al. 1995; Talos et al. 2006).”
BackgroundAgnati, L. F., Marcoli, M., Maura, G., Woods, A. S., & Guidolin, D. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1855-7 · Cited by 22 · see citing works
“These data have been the experimental background for introducing the new concept of ‘tetra-partite synapse’ for the complex formed by the classical synaptic contact of the glial processes (in particular the PAPs) surrounding them and, in addition, ECM peri-synaptic condensations (John et al. 2006; Dityatev et al. 2010…”
Wójtowicz, T., Brzdąk, P., & Mozrzymas, J. W. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00313 · Cited by 20 · see citing works
“Of note, tenascins can bind to neuronal sodium channels and play an important role in regulation of sodium channel density at axon initial segments (AISs) and nodes of Ranvier (Srinivasan et al., 1998).”
BackgroundInfluentialHermann, M., Reumann, R., Schostak, K., Kement, D., Gelderblom, M., Bernreuther, C., Frischknecht, R., Schipanski, A., Marik, S., Krasemann, S., et al. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103420 · Cited by 21 · see citing works
“2007), aggrecan (1:50, Millipore AB1031), brevican (1:50) (John et al. 2006), GFAP (1:500, Millipore MAB360), Iba1 (1:500, Wako 019-19741) or NeuN (1:50, Millipore MAB377) in blocking buffer containing 0,2 % Triton X-100.”
Self-citationSchott, B. H., Frischknecht, R., Dębska–Vielhaber, G., John, N., Behnisch, G., Düzel, E., Gundelfinger, E. D., & Seidenbecher, C. I. (2010) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2010.00142 · Cited by 20 · see citing works
Self-citationSchweitzer, B., Singh, J., Fejtova, A., Groc, L., Heine, M., & Frischknecht, R. (2017) · Scientific Reports · doi:10.1038/s41598-017-07003-3 · Cited by 19 · see citing works
Self-citationDo Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?
Lev‐Ram, V., Lemieux, S. P., Deerinck, T. J., Bushong, E. A., Perez, A. J., Pritchard, D. R., Toyama, B. H., Park, S. K. R., McClatchy, D. B., Savas, J. N., et al. (2024) · Cells · doi:10.3390/cells13191627 · Cited by 15 · see citing works
“…using light microscopy (LM) in cultured neurons [27] and in vivo [26], but this has never been confirmed by high-resolution 3D-EM. above observation has been reported using light microscopy (LM) in cultured neurons [27] and in vivo [26], but this has never been confirmed by high-resolution 3D-EM.”
BackgroundMethodSpatial patterns and cell surface clusters in perineuronal nets
Arnst, N., Kuznetsova, S., Lipachev, N., Shaikhutdinov, N., Melnikova, A., Олегович, М. М., Uvarov, P., Baltina, T., Rauvala, H., Osin, Y. N., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2016.07.020 · Cited by 15 · see citing works
“Accordingly, the diffusion rates of AMPA receptors in cultured hippocampal neurons are reduced between the 2 nd and 3 rd weeks in culture – at the time when the PNN-like structure is formed on the neuronal surface (Borgdorff and Choquet 2002; John et al., 2006).”
Neurocan regulates axon initial segment organization and neuronal activity
Baidoe‐Ansah, D., Mirzapourdelavar, H., Aleshin, S. E., Schott, B. H., Seidenbecher, C. I., Kaushik, R., & Dityatev, A. E. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.01.001 · Cited by 13 · see citing works
Self-citationHyalectanase Activities by the ADAMTS Metalloproteases
Fontanil, T., Mohamedi, Y., Casado, J. E., Obaya, Á. J., Cobo, T., & Cal, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062988 · Cited by 13 · see citing works
“This hyalectan is involved in physiological processes affecting brain plasticity, and it is located in perineuronal nets and in the axon initial segment [120].”
BackgroundStrackeljan, L., Baidoe‐Ansah, D., Mirzapourdelavar, H., Jia, S., Kaushik, R., Cangalaya, C., & Dityatev, A. E. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115186 · Cited by 14 · see citing works
Bahia, C. P., Houzel, J., Diniz, C. W. P., & Pereira, A. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21781 · Cited by 13 · see citing works
“The extracellular matrix (EM) of the brain is a rich source of a class of macromolecules known as proteoglycans, which are composed of glycosaminoglycan chains covalently bound to a protein core (Cooper and Steindler, 1986b; Ruoslahti, 1996; Rauch, 1997; John et al., 2006).”
BackgroundWanisch, K., Kovac, S., & Schorge, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053269 · Cited by 11 · see citing works
“It has been shown that between week 2 and 3 in vitro cultures start to build up the ECM which is similar to that of the adult brain and mainly based on HA and chondroitin sulphate proteoglycans, [45].”
The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro
Vijver, S. V. D., Missault, S., Soom, J. V., der Veken, P. V., Augustyns, K., Joossens, J., Dedeurwaerdere, S., & Giugliano, M. (2019) · PeerJ · doi:10.7717/peerj.6796 · Cited by 10 · see citing works
“We observed significant alterations in the collective emergent activity in vitro within just 1 h following the application of the SP inhibitor, consistent with the rapid in vivo action of ECM proteases (i.e., over minutes to hours (Wójtowicz, Brzdak & Mozrzymas, 2015)).”
BackgroundInfluentialBekku, Y., & Oohashi, T. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9636-7_8 · Cited by 8 · see citing works
Astrocyte‐derived factors regulate CNS myelination
Seiler, S., Rudolf, F., Gomes, F. R., Pavlovic, A., Nebel, J., Seidenbecher, C. I., & Foo, L. C. (2024) · Glia · doi:10.1002/glia.24596 · Cited by 6 · see citing works
“…mouse anti-SMI31 (Biolegend 801,601), 1:1000 rabbit anti-CASPR (Invitrogen PA5-68409), 1:500 guinea pig anti-BCAN was previously described by (John et al., 2006), 1:1000 goat anti-CNTN1 (EIAab P15020), 1:1000 rabbit anti-GFAP (DAKO Z0334), 1:1000 mouse anti-NF200 (Sigma N4142), 1:500 rabbit…”
Self-citationDynamic Organization of Neuronal Extracellular Matrix Revealed by HaloTag-HAPLN1
Sterin, I., Niazi, A., Kim, J. S., Park, J., & Park, S. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.0666-24.2024 · Cited by 9 · see citing works
Chondroitin Sulphate Proteoglycan Axonal Coats in the Human Mediodorsal Thalamic Nucleus
Pantazopoulos, H., Hossain, N. M., Chelini, G., Durning, P. T., Barbas, H., Zikopoulos, B., & Berretta, S. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.934764 · Cited by 5 · see citing works
An in vitro neuronal model replicating the in vivo maturation and heterogeneity of perineuronal netsPreprint
Dickens, S., Goodenough, A., & Kwok, J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.22.477344 · Cited by 5 · see citing works
Kim, S. Y., Jeon, J. C., Park, B., & Kim, D. E. (2025) · Neuroscience Letters · doi:10.1016/j.neulet.2025.138147 · Cited by 4 · see citing works
Singh, J. B., Perelló‐Amorós, B., Schneeberg, J., Mirzapourdelavar, H., Seidenbecher, C. I., Fejtová, A., Dityatev, A. E., & Frischknecht, R. (2025) · EMBO Reports · doi:10.1038/s44319-025-00644-w · Cited by 5 · see citing works
“Astrocytes play a critical role in synaptic plasticity and regulate several ECM proteins, including brevican (Favuzzi et al, 2017; Hamel et al, 2005; John et al, 2006).”
Self-citationA New Interpretative Paradigm for Conformational Protein Diseases
Agnati, L. F., Guidolin, D., Woods, A. S., Ciruela, F., Carone, C., Vallelunga, A., Escuela, D. O. B., Genedani, S., & Fuxé, K. (2013) · Current Protein and Peptide Science · doi:10.2174/1389203711314020006 · Cited by 4 · see citing works
Düsedau, H. P., Cangalaya, C., Stoyanov, S., Dityatev, A. E., & Dunay, I. R. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1616390 · Cited by 3 · see citing works
Cell-generated mechanical forces play a role in epileptogenesis after injury
Dalir, L., Tatic-Lucic, S., & Berdichevsky, Y. (2025) · bioRxiv · doi:10.1016/j.expneurol.2025.115376 · Cited by 2 · see citing works
“However, production of new ECM near the cells (John et al., 2006) could be expected to push beads away from the slice, while matrix degradation by matrix metalloproteases should result in release of beads into the culture medium.”
Cangalaya, C., Düsedau, H. P., Dunay, I. R., Dityatev, A. E., & Stoyanov, S. (2026) · Cells · doi:10.3390/cells15020182 · Cited by 2 · see citing works
“…#019-19741, 1:500; rat anti-CD68, Bio-Rad, Hercules, CA, USA, #MCA1957, 1:500; chicken anti-VGLUT1, Synaptic Systems, Göttingen, Germany, #135316, 1:1000; rabbit anti-aggrecan, Merck Millipore, Darmstadt, Germany, #AB1031, 1:1000; guinea pig anti-brevican, John et al., 2006 [23]) for 48 h at 4 ◦ C.”
- Authors
- John, N., Krügel, H., Frischknecht, R., Smalla, K.-H., Schultz, C., Kreutz, M. R., Gundelfinger, E. D., & Seidenbecher, C. I.
- Affiliations
- Leibniz Institute for Neurobiology (DE)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Goethe University Frankfurt (DE)
- Corresponding author
- Seidenbecher, Constanze I.
- ORCID
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 31
- Issue
- 4
- Pages
- 774-784
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1965503179
- Cited by
- 122
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 2 · 2015: 10 · 2014: 6 · 2013: 5 · 2012: 7
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- perineuronal nets, brevican, chondroitin sulfate proteoglycans, extracellular matrix, hippocampus, astrocytes, glial fibrillary acidic protein, synapses, axon initial segment, Vicia villosa lectin, primary neuronal cultures
- MeSH terms
- Animals, Cells, Cultured, Extracellular Matrix, Hippocampus, Humans, Monensin, Nerve Tissue Proteins, Neuroglia, Neurons, Chondroitin Sulfate Proteoglycans, Synapses, Biomarkers, Coculture Techniques, Protein Isoforms, Lectins, C-Type, Rats, Brevican
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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