ArticleBrain research bulletin2022
Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice.
Article in Brain research bulletin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- 4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP/PS1 mouse model.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic Regulation of Hyaluronan-Associated Genes in the Brain: Identifying Key Regulatory Sites.Epigenomes · 2026Review
- Inhibitor of hyaluronic acid synthesis 4-methylumbelliferone (4-MU) as a potential anti-inflammatory substance in acute neuroinflammation model in vivo.Inflammopharmacology · 2026Article
- Midbrain extracellular matrix and microglia are associated with cognition in aging mice.Nature communications · 2025Article
- Estrogenic regulation of perineuronal nets in the mouse insular cortex and hippocampus.Neuropharmacology · 2025Article
- Intestinal Ischemia/Reperfusion Injury Influences Hyaluronan Homeostasis in the Rat Brain.International journal of molecular sciences · 2025Article
- 4-Methylumbelliferone (4-MU) Improves Learning and Memory After Cerebral Ischemia/Reperfusion Injury in Rats.Behavioural neurology · 2025Article
- Perineuronal Nets: From Structure to Neurological Disorders.Current medicinal chemistry · 2025Review
- 4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study.Archives of academic emergency medicine · 2025Article
- Modulation of stress-, pain-, and alcohol-related behaviors by perineuronal nets.Neurobiology of stress · 2024Article
- Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence.International journal of molecular sciences · 2024Review
- Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders.International journal of molecular sciences · 2024Review
- Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury.Scientific reports · 2023Article
- CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice.Neurobiology of disease · 2023Article
- 4-Methylumbeliferone Treatment at a Dose of 1.2 g/kg/Day Is Safe for Long-Term Usage in Rats.International journal of molecular sciences · 2023Article
- Hyaluronan in the Cancer Cells Microenvironment.Cancers · 2023Review
- Matrix disequilibrium in Alzheimer's disease and conditions that increase Alzheimer's disease risk.Frontiers in neuroscience · 2023Review
- Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Hyaluronan (HA) is a core constituent of perineuronal nets (PNNs) that surround subpopulations of neurones. The PNNs control synaptic stabilization in both the developing and adult central nervous system, and disruption of PNNs has shown to reactivate neuroplasticity. We investigated the possibility of memory prolongation by attenuating PNN formation using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis. Adult C57BL/6 mice were fed with chow containing 5% (w/w) 4-MU for 6 months, at a dose ~6.7 mg/g/day. The oral administration of 4-MU reduced the glycosaminoglycan level in the brain to 72% and the spinal cord to 50% when compared to the controls. Spontaneous object recognition test (SOR) performed at 2, 3, 6 and 7 months showed a significant increase in SOR score in the 6-months treatment group 24 h after object presentation. The effect however did not persist in the washout group (1-month post treatment). Immunohistochemistry confirmed a reduction of PNNs, with shorter and less arborization of aggrecan staining around dendrites in hippocampus after 6 months of 4-MU treatment. Histopathological examination revealed mild atrophy in articular cartilage but it did not affect the motor performance as demonstrated in rotarod test. In conclusion, systemic oral administration of 4-MU for 6 months reduced PNN formation around neurons and enhanced memory retention in mice. However, the memory enhancement was not sustained despite the reduction of PNNs, possibly due to the lack of memory enhancement training during the washout period. Our results suggest that 4-MU treatment might offer a strategy for PNN modulation in memory enhancement.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.