Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
Abstract
Extracellular matrix molecules accumulate around central nervous system neurons during postnatal development, forming so‐called perineuronal nets (PNNs). PNNs play a role in restricting plasticity at the end of critical periods. In the adult rat cerebellum, PNNs are found around large, deep cerebellar nuclei (DCN) neurons and Golgi neurons and are composed of chondroitin sulfate proteoglycans (CSPGs), tenascin‐R (TN‐R), hyaluronan (HA), and link proteins, such as cartilage link protein 1 (Crtl1). Granule cells and Purkinje cells are surrounded by a partially organized matrix. Both glial cells and neurons surrounded by PNNs are the site of synthesis of some CSPGs and of TN‐R, but only neurons produce HA synthetic enzymes (HASs), thus HA, and link proteins, which are scaffolding molecules for an organized matrix. To elucidate the mechanisms of formation of PNNs, we analyzed by immunohistochemistry and in situ hybridization which PNN components are upregulated during PNN formation in rat cerebellar postnatal development and what cell types express them. We observed that Wisteria floribunda agglutinin‐binding PNNs develop around DCN neurons from postnatal day (P)7 and around Golgi neurons from P14. At the same time as their PNNs start to form, these neurons upregulate aggrecan, Crtl1, and HASs mRNAs. However, Crtl1 is the only PNN component to be expressed exclusively in neurons surrounded by PNNs. The other link protein that shows a perineuronal net pattern in the DCN, Bral2, is upregulated later during development. These data suggest that aggrecan, HA, and, particularly, Crtl1 might be crucial elements for the initial assembly of PNNs. J. Comp. Neurol. 501:83–94, 2007. © 2007 Wiley‐Liss, Inc.
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PNN maturation occurs in an experience-dependent manner, requiring neuronal activation through glutamatergic excitation, availability of key PNN components, expression on neurons of ECM surface receptors, and transcription factors inducing neuronal maturation.
“Their maturation occurs in an experience-dependent manner, requiring (i) neuronal activation through glutamatergic excitation,78 (ii) availability of key PNN components, such as specific CSPGs, link proteins and tenascin R, (iii) expression on neurons of ECM surface receptors79, 80 and (iv) transcription factors inducing neuronal maturation.25, 38”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [79]
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- Authors
- Carulli, D., Rhodes, K. E., & Fawcett, J. W.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Fawcett, James W.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2007-01-05
- Volume
- 501
- Issue
- 1
- Pages
- 83-94
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2030127666
- Cited by
- 158
- References
- 60
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 3 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 8 · 2013: 12 · 2012: 9
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- perineuronal nets, cerebellum, deep cerebellar nuclei, aggrecan, hyaluronan synthase, hyaluronic acid, extracellular matrix, chondroitin sulfate proteoglycans, tenascin-R, postnatal development, Wisteria floribunda agglutinin
- MeSH terms
- Hyaluronan Synthases, Proteoglycan Link Protein, Aging, Animals, Animals, Newborn, Cerebellar Nuclei, Cerebellum, Female, Golgi Apparatus, Immunohistochemistry, Nerve Net, Neurons, Proteoglycans, RNA, Messenger, Time Factors, Glucuronosyltransferase, Up-Regulation, Extracellular Matrix Proteins, Rats, Sprague-Dawley, In Situ Hybridization, Receptors, N-Acetylglucosamine, Plant Lectins, Rats, Aggrecans
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