Brain Barriers and a Subpopulation of Astroglial Progenitors of Developing Human Forebrain Are Immunostained for the Glycoprotein YKL-40

Abstract

SummaryYKL-40, a glycoprotein involved in cell differentiation, has been associated with neurodevelopmental disorders, angiogenesis, neuroinflammation and glioblastomas. We evaluated YKL-40 protein distribution in the early human forebrain using double-labeling immunofluorescence and immunohistochemistry. Immunoreactivity was detected in neuroepithelial cells, radial glial end feet, leptomeningeal cells and choroid plexus epithelial cells. The subpial marginal zone was YKL-40-positive, particularly in the hippocampus, from an early beginning stage in its development. Blood vessels in the intermediate and subventricular zones showed specific YKL-40 reactivity confined to pericytes. Furthermore, a population of YKL-40-positive, small, rounded cells was identified in the ventricular and subventricular zones. Real-time quantitative RT-PCR analysis showed strong YKL-40 mRNA expression in the leptomeninges and the choroid plexuses, and weaker expression in the telencephalic wall. Immunohistochemistry revealed a differential distribution of YKL-40 across the zones of the developing telencephalic wall. We show that YKL-40 is associated with sites of the brain barrier systems and propose that it is involved in controlling local angiogenesis and access of peripheral cells to the forebrain via secretion from leptomeningeal cells, choroid plexus epithelium and pericytes. Furthermore, we suggest that the small, rounded, YKL-40-positive cells represent a subpopulation of astroglial progenitors, and that YKL-40 could be involved in the differentiation of a particular astrocytic lineage. (J Histochem Cytochem 62:369-388, 2014)

Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures

“…The reported high expression levels for CYP1B1 and CH31L1 in the BBB suggest a role for these genes in BBB function (Safran et al, 2010; Decleves et al, 2011; Bjørnbak et al, 2014). CHI3L1 is also an astroglial lineage marker, and AREG acts as a growth factor and mitogen in astrocytes (Safran et al, 2010; Bjørnbak et al, 2014). RAB27B is involved in axonal anterograde transport (Arimura et al, 2009).…”

Outer brain barriers in rat and human development

“…The embryos and the fetuses were obtained from legal abortions, as previously described (Bjørnbak et al, 2014). The adult brain samples were donated for research following neurosurgery.…”

Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone

“…So far, YKL-40 has been found to induce tight interplay between the membrane receptors syndecan-1 and an adjacent membrane-associated protein integrin αvβ5 [21] on endothelial cells [70,71], and triggered a signaling cascade through pFAK [8,61] to MAP kinase ERK-1 and ERK-2 by regulating VEGF expression and inducing angiogenesis as an independent angiogenic factor under hypoxic conditions.…”

“…Glioblastoma has an incidence that increases with age and peaks between 75 and 84 years old, being more common in white males, according to the most recent Central Brain Tumor Registry of the United States (CBTRUS) statistical report. The median survival for patients diagnosed with GB using the current standard of care is only 12 to 15 months [8,52,77,81] despite multimodality treatment with aggressive microsurgical resection, combined radiation and chemotherapy, and adjuvant chemotherapy [81]. GB cells are diffusely infiltrative and motile; consequently, GB renders them incurable by surgery alone [24,78,79].…”