"Brevican (BCAN) ... and growth differentiation factor 15 ... showed the most significant, and multiple, associations with dementia, stroke and movement functions."
https://www.nature.com/articles/s43587-024-00753-6
"Brevican is a secreted member of the lectican/hyalectan family of hyaluronan-binding chondroitin sulfate proteoglycans (CSPGs; (Faissner et al., 2010)). Mediated by binding of homologous C-type lectin motifs in the C-terminal domain, brevican comprises a structural factor of the ECM together with tenascins and hyalurolan (Bekku et al., 2009). It is predominantly present in perineuronal nets (PNNs) of the adult CNS and is transiently expressed by neurons during development."
https://www.sciencedirect.com/science/article/pii/S0301008216300478
#glycobiology #perineuronalnets #neuroscience #aging #ExtracellularMatrix
Using proteomics and imaging data from UK Biobank, the authors identified multiple circulating proteins associated with brain aging and discovered undulating age-related changes in the plasma proteome, with peaks occurring at 57, 70 and 78 years of age.
Really cool detail on #perineuronalnets: Not only do the holes contain (stabilized) synapses, but those synapses are also tripartite - i.e. they are also contacted by Astrocytes. PNNs constrain the Astrocyte's leaflets, and prevent them from spreading off-synapse. This prevents glutamate spillover and mGluR activation.
Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice
Tewari et al., Nature Neuroscience 2024
https://doi.org/10.1038/s41593-024-01714-3
Really cool! This technique - tomoelastography - measures the mechanical stiffness of tissue.
"The cerebral cortex, i.e. the outer layer of the brain consisting of gray matter, is less stiff in people affected by MS than in healthy people. The animal model showed that this is due to changes in the perineuronal networks. Perineuronal nets form a network that surrounds the neurons and that loosens when there is inflammation." (translation by Google)
I have often wondered if there are differences in perineuronal nets in people with connective tissue disorders. Could this technique detect differences in people with EDS, for example? What about its use in other parts of the body, besides the brain? Perhaps the gut?
Also, changes in PNN occur with aging. Could this technique be used to measure brain aging?
#MultipleSclerosis #EDS #EhlersDanlos #ConnectiveTissue #Aging
#Tomoelastography #PerineuronalNets
Rhyothemis
Moritz Negwer