Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum
Abstract
Perineuronal nets (PNNs) are pericellular coats of condensed matrix that enwrap the cell bodies and dendrites of many adult central nervous system (CNS) neurons. These extracellular matrices (ECMs) play a structural role as well as instructive roles in the control of CNS plasticity and the termination of critical periods. The cartilage link protein Crtl1/Hapln1 was reported to be a trigger for the formation of PNNs in the visual cortex. Bral2/Hapln4 is another link protein that is expressed in PNNs, mainly in the brainstem and cerebellum. To assess the role of Bral2 in PNN formation, we examined the expression of PNN components in targeted mouse mutants lacking Bral2. We show here that Bral2‐deficient mice have attenuated PNNs, but the overall levels of chondroitin sulfate proteoglycans, lecticans, are unchanged with the exception of neurocan. Bral2 deficiency markedly affected the localization of brevican in all of the nuclei tested, and neurocan concomitant with Crtl1 in some of the nuclei, whereas no effect was seen on aggrecan even with the attenuation of Crtl1. Bral2 may have a role in the organization of the PNN, in association with brevican, that is independent of aggrecan binding. There was a heterogenous attenuation of PNN components, including glycosaminoglycans, indicating the elaborate molecular organization of the PNN components. Strikingly, a slight decrease in the number of synapses in deep cerebellar nuclei neurons was found. Taken together, these results imply that Bral2‐brevican interaction may play a key role in synaptic stabilization and the structural integrity of the PNN. J. Comp. Neurol. 520:1721–1736, 2012. © 2011 Wiley Periodicals, Inc.
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Perineuronal nets are composed of chondroitin sulphate proteoglycans, including lecticans, phosphacan, hyaluronan, tenascin-R and link proteins.
“PNs are composed of chondroitin sulphate proteoglycans (CSPGs), including lecticans (aggrecan, brevican, neurocan and versican), phosphacan and hyaluronan, TN-R and link proteins (cartilage link protein Crtl-1/HAPLN-1 and brain link protein Bral2/HAPLN-4).11, 12, 13, 14”
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 [14]
In mutant mice lacking Hapln4/Bral2, perineuronal nets in the brainstem and cerebellum are reduced, with complete lack of brevican and general attenuation of most other PNN components.
“Similarly, in mutant mice lacking Hapln4/Bral2, which is mainly expressed in the brainstem and cerebellum, PNNs in these areas are reduced, with a complete lack of brevican and a general attenuation of the majority of the other PNN components (Bekku et al., 2012).”
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 Bekku et al., 2012
Aggrecan binding in perineuronal nets is independent, as shown by lack of attenuation of aggrecan PNN formation even at the same neuronal surface.
“However, there was no attenuation in the PNN formation of aggrecan even at the same neuronal surface, which indicate the independent binding of aggrecan in the PNN.”
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 Bekku et al., 2012
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- Authors
- Bekku, Y., Saito, M., Moser, M., Fuchigami, M., Maehara, A., Nakayama, M., Kusachi, S., Ninomiya, Y., & Oohashi, T.
- Affiliations
- Okayama University (JP)
- Max Planck Society (DE)
- Corresponding author
- Oohashi, Toshitaka
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2012-04-02
- Volume
- 520
- Issue
- 8
- Pages
- 1721-1736
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2100322061
- Cited by
- 65
- References
- 57
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 8 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22659323, 22591686, 24659590, 23592164, 23390348)
- 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, brevican, HAPLN1, link protein, extracellular matrix, neurocan, aggrecan, glycosaminoglycans, deep cerebellar nuclei, brainstem, synaptic stabilization
- MeSH terms
- Proteoglycan Link Protein, Animals, Brain Stem, Cerebellum, Extracellular Matrix, Immunohistochemistry, Mice, Inbred C57BL, Nerve Tissue Proteins, Synapses, Blotting, Southern, Blotting, Northern, Extracellular Matrix Proteins, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Mice, Brevican, Real-Time Polymerase Chain Reaction
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