ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93 citing papers in PubMed, 150 citations in OpenAlex.
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- Intestinal Ischemia/Reperfusion Injury Influences Hyaluronan Homeostasis in the Rat Brain.International journal of molecular sciences · 2025Article
- The Effects of miR-22-3p on Differentiation of Human Dental Pulp Stem Cells into Neural Progenitor-Like Cells.Molecular neurobiology · 2025Article
- Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Preventing epileptogenesis by interaction between inositol isomers and proteins.Epilepsia open · 2025Article
- Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice.Nature neuroscience · 2024Article
- Genetic Deficiencies of Hyaluronan Degradation.Cells · 2024Review
- Increased expression of chondroitin sulfate proteoglycans in dentate gyrus and amygdala causes postinfectious seizures.Brain : a journal of neurology · 2024Article
- Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes.Frontiers in neural circuits · 2024Article
- Postischemic Infusion of Apigenin Reduces Seizure Burden in Preterm Fetal Sheep.International journal of molecular sciences · 2023Article
- BubbleDrive, a low-volume incubation chamber for acute brain slices.Scientific reports · 2023Article
- Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke.Journal of biomedical science · 2023Article
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10 authors at 6 institutions in 3 countries.
Funding
Abstract
Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3(-/-) mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3(-/-), Has1(-/-), and Has2(CKO), the seizures were most prevalent in Has3(-/-) mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3(-/-) brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by ∼ 40% in Has3(-/-) mice. Finally, osmotic manipulation experiments in brain slices from Has3(-/-) and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments.
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