"MC_PC_16050"
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Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.
- MeSH
- chondroitinsulfáty * MeSH
- extracelulární matrix MeSH
- mozek MeSH
- myši MeSH
- neuroplasticita * MeSH
- stárnutí MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The perineuronal net (PNN) is a specialized extracellular matrix structure that surrounds subpopulations of neurons in the central nervous system (CNS). The appearance of PNNs on the cell surface marks the closure of the critical period during development and has been observed to reduce synaptic plasticity. Perineuronal nets comprise hyaluronan, chondroitin sulfate proteoglycans (CSPGs), link proteins, tenascin-R, and other components, some of which are substrates for a disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs (ADAMTS) proteases. There is a high heterogeneity of PNNs in the CNS. Depending on which part of the CNS is studied, the PNNs may be observed surrounding the soma, or both the soma and proximal dendrites. The most robust marker for PNN is a lectin called Wisteria floribunda agglutinin. Here, we describe a method for preparing tissue for visualization of PNNs in CNS.
The perineuronal net (PNN) is a mesh-like proteoglycan structure on the neuronal surface which is involved in regulating plasticity. The PNN regulates plasticity via multiple pathways, one of which is direct regulation of synapses through the control of AMPA receptor mobility. Since neuronal pentraxin 2 (Nptx2) is a known regulator of AMPA receptor mobility and Nptx2 can be removed from the neuronal surface by PNN removal, we investigated whether Nptx2 has a function in the PNN. We found that Nptx2 binds to the glycosaminoglycans hyaluronan and chondroitin sulphate E in the PNN. Furthermore, in primary cortical neuron cultures, the addition of NPTX2 to the culture medium enhances PNN formation during PNN development. These findings suggest Nptx2 as a novel PNN binding protein with a role in the mechanism of PNN formation.
- MeSH
- C-reaktivní protein metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- nervová síť chemie cytologie metabolismus MeSH
- neurony chemie metabolismus MeSH
- neuroplasticita fyziologie MeSH
- perineuronální satelitní buňky chemie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- proteiny nervové tkáně metabolismus MeSH
- vazba proteinů fyziologie MeSH
- zrakové korové centrum chemie cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
With an increasingly aging global population, the incidence of neurological diseases such as dementia is set to increase to unmanageable levels, yet there are currently only symptomatic therapies available for treatment. The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Specifically, condensed mesh-like structures called perineuronal nets (PNNs) form around subsets of neurons and have a profound effect on axonal growth and limit neuronal plasticity. These PNNs act as a morphological checkpoint and can influence memory and cognition. Manipulating these important ECM structures may provide the key to reactivating plasticity and restoring memory, both of which are severely impaired in AD and other associated neurological diseases. This review explores the current understanding of how PNNs are manipulated and examines potential new methods for PNN modulation. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.
- MeSH
- extracelulární matrix fyziologie MeSH
- lidé MeSH
- neurony fyziologie MeSH
- neuroplasticita * MeSH
- paměť * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
