ArticleEpilepsia open2024
Age-dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy.
Article in Epilepsia open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- Mechanical characterization of human versus porcine brain tissue under large strains.Biomechanics and modeling in mechanobiology · 2026Article
- Extracellular matrix and perineuronal nets in neural plasticity, memory, and epileptogenesis.Frontiers in molecular neuroscience · 2026Review
- Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations.Frontiers in molecular neuroscience · 2026Article
- Perineuronal nets in the developing brain: implications for neurodevelopmental disorders.Molecular brain · 2025Review
- Characterization of Perineuronal Nets in the Paraventricular Nucleus of the Hypothalamus and their Alteration in Neurogenic Hypertension.Cellular and molecular neurobiology · 2025Article
- Critical Periods and Beyond: Dynamic Functions of Perineuronal Nets in Cognition, Development, and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Increased levels of HAPLN2, which anchors dense extracellular matrix, in the hippocampus of APOE4 targeted replacement mice.bioRxiv : the preprint server for biology · 2025Article
- Characterization of Perineuronal Nets (PNNs) in the Paraventricular Nucleus of the Hypothalamus (PVN) and their alteration in neurogenic hypertension.Research square · 2025Article
- Contribution of perineuronal nets to hyperexcitability in pilocarpine-induced status epilepticus.Epilepsia · 2025Article
- A sensitive period for the development of episodic-like memory in mice.Current biology : CB · 2025Article
- Review
- Age-dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy.Epilepsia open · 2024Article
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14 authors.
Funding
Abstract
objectivePerineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age-dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age-matched post-mortem control subjects and to compare PNN-related changes with memory impairment observed in our patient cohort.
methodsSixty-six formalin-fixed and paraffin-embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty-nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum.
resultsPNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age-matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p < 0.05). SIGNIFICANCE: Our results were compatible with age-dependent ECM specialization in the human hippocampus and its precocious aging in the epileptic condition. These observations confirm recent experimental animal models and also support the notion that PNN play a role in memory formation in the human brain. PLAIN LANGUAGE SUMMARY: "Perineuronal nets" (PNN) are a specialized compartment of the extracellular matrix (ECM), especially surrounding highly active neurons of the mammalian brain. There is evidence that PNN play a role in memory formation, brain maturation, and in some pathologies like Alzheimer's disease, schizophrenia or epilepsy. In this study, we investigated the role of PNN in patients suffering from drug-resistant focal epilepsy compared to controls. We found that with increasing age, more neurons are surrounded by PNN. Similarly, all epilepsy patients but especially patients with better memory performance also had more PNN. This study raises further interest in studying ECM molecules in the human brain under physiological and pathophysiological conditions.
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