Persistent decrease in multiple components of the perineuronal net following status epilepticus
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In the rodent model of temporal lobe epilepsy, there is extensive synaptic reorganization within the hippocampus following a single prolonged seizure event, after which animals eventually develop epilepsy. The perineuronal net (PN), a component of the neural extracellular matrix (ECM), primarily surrounds inhibitory interneurons and, under normal conditions, restricts synaptic reorganization. The objective of the current study was to explore the effects of status epilepticus (SE) on PNs in the adult hippocampus. The aggrecan component of the PN was studied, acutely (48 h post‐SE), sub‐acutely (1 week post‐SE) and during the chronic period (2 months post‐SE). Aggrecan expressing PNs decreased by 1 week, likely contributing to a permissive environment for neuronal reorganization, and remained attenuated at 2 months. The SE‐exposed hippocampus showed many PNs with poor structural integrity, a condition rarely seen in controls. Additionally, the decrease in the aggrecan component of the PN was preceded by a decrease in hyaluronan and proteoglycan link protein 1 (HAPLN1) and hyaluronan synthase 3 (HAS3), which are components of the PN known to stabilize the connection between aggrecan and hyaluronan, a major constituent of the ECM. These results were replicated in vitro with the addition of excess KCl to hippocampal cultures. Enhanced neuronal activity caused a decrease in aggrecan, HAPLN1 and HAS3 around hippocampal cells in vivo and in vitro, leaving inhibitory interneurons susceptible to increased synaptic reorganization. These studies are the foundation for future experiments to explore how loss of the PN following SE contributes to the development of epilepsy.
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A number of seizure models show downregulation of the PNN components aggrecan, hyaluronan and proteoglycan link protein 1 (HAPLN1) and hyaluronan synthease-3.
“Indeed a number of seizure models show downregulation of the PNN components aggrecan, hyaluronan and proteoglycan link protein 1 (HAPLN1) and hyaluronan synthease-343.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [43]
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- Authors
- McRae, P. A., Baranov, E., Rogers, S. L., & Porter, B. E.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2012-08-31
- Volume
- 36
- Issue
- 11
- Pages
- 3471-3482
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC4058987
- OpenAlex
- W1531000242
- Cited by
- 85
- References
- 54
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 5 · 2015: 8 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS056222, T32NS007413)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- perineuronal nets, status epilepticus, temporal lobe epilepsy, hippocampus, extracellular matrix, aggrecan, hyaluronic acid, HAPLN1, HAS3, inhibitory interneurons, synaptic remodeling, neuronal activity, epilepsy development
- MeSH terms
- Hyaluronan Synthases, Proteoglycan Link Protein, Animals, Extracellular Matrix, Hippocampus, Hyaluronic Acid, Interneurons, Male, Potassium Chloride, Proteoglycans, Status Epilepticus, Glucuronosyltransferase, Extracellular Matrix Proteins, Rats, Sprague-Dawley, Rats, Aggrecans
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