The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index.
Perineuronal net formation and structure in aggrecan knockout mice
Open accessAbstract
Perineuronal nets (PNNs) are specialized substructures of the neural extracellular matrix (ECM) which envelop the cell soma and proximal neurites of particular sets of neurons with apertures at sites of synaptic contact. Previous studies have shown that PNNs are enriched with chondroitin sulfate proteoglycans (CSPGs) and hyaluronan, however, a complete understanding of their precise molecular composition has been elusive. In addition, identifying which specific PNN components are critical to the formation of this structure has not been demonstrated. Previous work in our laboratory has demonstrated that the CSPG, aggrecan, is a key activity-dependent component of PNNs in vivo. In order to assess the contribution of aggrecan to PNN formation, we utilized cartilage matrix deficiency (cmd) mice, which lack aggrecan. Herein, we utilized an in vitro model, dissociated cortical culture, and an ex vivo model, organotypic slice culture, to specifically investigate the role aggrecan plays in PNN formation. Our work demonstrates that staining with the lectin, Wisteria floribunda agglutinin (WFA), considered a broad PNN marker, is eliminated in the absence of aggrecan, suggesting the loss of PNNs. However, in contrast, we found that the expression patterns of other PNN markers, including hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R, brevican, and hyaluronan are unaffected by the absence of aggrecan. Lastly, we determined that while all PNN components are bound to the surface in a hyaluronan-dependent manner, only HAPLN1 remains attached to the cell surface when neurons are treated with chondroitinase. These results suggest a different model for the molecular association of PNNs to the cell surface. Together our work has served to assess the contribution of aggrecan to PNN formation while providing key evidence concerning the molecular composition of PNNs in addition to determining how these components ultimately form PNNs.
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In the citing paper
“ChABC degrades chondroitin sulfate proteoglycans, which are a major component of the PNNs (32).”
From Perineuronal nets protect fast-spiking interneurons against oxidative stress (2013) · cites this paper as [32]
In the citing paper
“cortical primary neurons derived from aggrecan--deficient mice are abnormal in that they are not stained by the lectin Wisteria floribunda agglutinin (WFA), a broad PNN marker, indicating an essential role of aggrecan in PNN formation (Giamanco et al., 2010).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Giamanco et al., 2010
In the citing paper
“heterozygote aggrecan-deficient (ACAN+/−) mice”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [36]
In the citing paper
“Aggrecan is a major component of the brain ECM and of at least a subgroup of PNNs, and contains numerous CS chains with a predominant CS-6 representation.45, 46”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [45]
In the citing paper
“Reports that aggrecan knockout results in loss of WFA-positive PNNs45, 46 support this possibility.”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [45]
In the citing paper
“Together, these findings indicate that WFA may not detect CS-6 sulfation patterns, at least not those recognized by 3B3 and CS56, and may label only some forms of aggrecan (see below).45”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [45]
In the citing paper
“Notably, aggrecan is necessary for PNN formation, as shown in the HEK cell model (Kwok et al., 2010) and in organotypic cultures derived from aggrecan knockout mice (Giamanco et al., 2010).”
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 Giamanco et al., 2010
Citations
Cites
Hyaluronan: from extracellular glue to pericellular cue
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Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
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Organotypic slice cultures: a technique has come of age
Gähwiler, B. H. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01122-3 · Cited by 884
Lecticans: organizers of the brain extracellular matrix
Yamaguchi, Y. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000690 · Cited by 642
Proteoglycans in the Developing Brain: New Conceptual Insights for Old Proteins
Bandtlow, C. E., & Zimmermann, D. R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.4.1267 · Cited by 632
Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex
Hendry, S., Schwark, H. D., Jones, E. G., & Yan, J. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-05-01503.1987 · Cited by 601
Perineuronal nets: past and present
Celio, M. R., Spreafico, R., De Biasi, S., & Vitellaro-Zuccarello, L. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01298-3 · Cited by 497
Animals lacking link protein have attenuated perineuronal nets and persistent plasticity
Carulli, D., Pizzorusso, T., Kwok, J. C. F., Putignano, E., Poli, A., Forostyak, S., Andrews, M. R., Deepa, S. S., Glant, T. T., & Fawcett, J. W. (2010) · Brain · doi:10.1093/brain/awq145 · Cited by 495
Extracellular matrix of the central nervous system: from neglect to challenge
Zimmermann, D. R., & Dours-Zimmermann, M. T. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0485-9 · Cited by 465
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Items 201–207 of 207
The Effect of Dopamine on Neuroplasticity in Spinal Cord Injury
Chesnokov, A. A., Kalinina, D. S., Makhortykh, A. E., Khuzin, D. V., & Евгеньевич, М. П. (2025) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093025040015
The role of perineuronal nets in post-stroke neuroplasticity and functional reorganization
Aderinto, N., Abraham, I. C., Kwape, J. M., Gaur, A., Akanbi, C. A., Oyeniyi, D. T., Babalola, A. E., Babalola, D. O., Adeyeye, J., Bukky, S. O., et al. (2025) · Next research. · doi:10.1016/j.nexres.2025.101060
Synaptic changes upon removal of extracellular perineuronal nets in adult mouse visual cortex
Faini, G. (2017) · theses.fr (ABES) · doi:10.70675/7b38d504z7edfz47dezbf9az0a8668ae448a
Devienne, G. F. (2019) · theses.fr (ABES) · doi:10.70675/453418efzc908z49e0zba6fz71fefaa50691
Douceau, S. (2020) · theses.fr (ABES) · doi:10.70675/6f1007f2z8468z4365zb07dz7d863bf32cd5
Belz, L., Aouci, R., Allain, B., Henderson, F., Fontaine, A., Desgagne, P., Calzaroni, L., Fabre, V., Pardi, M. B., Levi, G., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.23.740286
Metadata
- Authors
- Giamanco, K. A., Morawski, M., & Matthews, R. T.
- Affiliations
- SUNY Upstate Medical University (US)
- Leipzig University (DE)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 170
- Issue
- 4
- Pages
- 1314-1327
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2033004840
- Cited by
- 207
- References
- 77
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 13 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 15 · 2019: 9 · 2018: 17 · 2017: 16 · 2016: 15 · 2015: 14 · 2014: 12 · 2013: 11 · 2012: 17
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- 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, aggrecan, chondroitin sulfate proteoglycans, hyaluronic acid, HAPLN1, tenascin-R, brevican, Wisteria floribunda agglutinin, chondroitinase, organotypic slice cultures
- MeSH terms
- Proteoglycan Link Protein, Animals, Cells, Cultured, Chondroitin Sulfates, Extracellular Matrix, gamma-Aminobutyric Acid, Hyaluronic Acid, Interneurons, Neurons, Parvalbumins, Proteoglycans, Extracellular Matrix Proteins, Mice, Knockout, Tenascin, Mice, Aggrecans, In Vitro Techniques
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