Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability

Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability.ISSN:0271-678XISSN:1559-701

Healing Animals, Feeding Souls: Ethnobotanical Values at Sacred Sites in Central Italy

Ethnobotanical knowledge is a fundamental repository of the values and applications of different plants. This knowledge is often related to spiritual beliefs and religious sites, where plants have been nurtured and conserved for their use in rituals and traditional practices. While this link is well known for different areas of the global south, it has hardly been investigated in relatively more secular and modernized Western contexts. Here, we use first–hand vegetation surveys and published records to examine the occurrence of ethnobotanical values at 30 Catholic shrines in Central Italy, and compare them with an equal number of non–sacred control sites. We ask this: to what extent is there an association of useful plants with sacred places in Italy, as found in other cultural contexts? We show that a greater number of useful plants are found at sacred sites. While this is mainly a consequence of the higher species richness of sacred sites, an association with plants used in animal husbandry is particularly evident, and likely related to the deep historical connection between sacred places and pastoralist traditions in Central Italy. Also, we show that there are significant variations in the distribution of old trees; the largest specimens are found at the center of sacred sites, while tree size visibly decreases away from the shrines. This indicates also that individual trees have been actively managed and conserved at sacred sites, probably driven by the symbolic values that old trees frequently embody

sj-pdf-2-jcb-10.1177_0271678X231216270 - Supplemental material for Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Supplemental material, sj-pdf-2-jcb-10.1177_0271678X231216270 for Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability by Ruslan Rust, Mea M Holm, Matteo Egger, Oliver Weinmann, Daniёlle van Rossum, Fruzsina R Walter, Ana Raquel Santa-Maria, Lisa Grönnert, Michael A Maurer, Simon Kraler, Alexander Akhmedov, Rose Cideciyan, Thomas F Lüscher, Maria A Deli, Inge K Herrmann and Martin E Schwab in Journal of Cerebral Blood Flow & Metabolism</p

sj-pdf-1-jcb-10.1177_0271678X231216270 - Supplemental material for Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231216270 for Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability by Ruslan Rust, Mea M Holm, Matteo Egger, Oliver Weinmann, Daniёlle van Rossum, Fruzsina R Walter, Ana Raquel Santa-Maria, Lisa Grönnert, Michael A Maurer, Simon Kraler, Alexander Akhmedov, Rose Cideciyan, Thomas F Lüscher, Maria A Deli, Inge K Herrmann and Martin E Schwab in Journal of Cerebral Blood Flow & Metabolism</p