Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis

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dc.contributor.authorMontserrat Guerra, Maria
dc.contributor.authorHenzi, Roberto
dc.contributor.authorOrtloff Trautmann, Alexander
dc.contributor.authorLichtin, Nicole
dc.contributor.authorVio, Karin
dc.contributor.authorJimenez, Antonio J.
dc.contributor.authorDolores Dominguez Pinos, Maria
dc.contributor.authorGonzalez, Cesar
dc.contributor.authorClara Jara, Maria
dc.contributor.authorHinostroza, Fernando
dc.contributor.authorRodriguez, Sara
dc.contributor.authorJara, Maryoris
dc.contributor.authorOrtega, Eduardo
dc.contributor.authorGuerra, Francisco
dc.contributor.authorSival, Deborah A.
dc.contributor.authorden Dunnen, Wilfred F. A.
dc.contributor.authorPerez Figares, Jose M.
dc.contributor.authorMcAllister, James P.
dc.contributor.authorJohanson, Conrad E.
dc.contributor.authorRodriguez, Esteban M.
dc.date2015
dc.date.accessioned2021-04-30T17:06:06Z
dc.date.available2021-04-30T17:06:06Z
dc.description.abstractFetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.
dc.identifier.citationJOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY,Vol.74,653-671,2015
dc.identifier.doi10.1097/NEN.0000000000000203
dc.identifier.urihttp://repositoriodigital.uct.cl/handle/10925/4028
dc.language.isoen
dc.publisherOXFORD UNIV PRESS INC
dc.sourceJOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
dc.subject.englishCerebrospinal fluid
dc.subject.englishCongenital hydrocephalus
dc.subject.englishHTx rat
dc.subject.englishHuman
dc.subject.englishJunction pathology
dc.subject.englishNeural stem cells
dc.subject.englishNeurospheres
dc.subject.englishVentricular zone disruption
dc.titleCell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis
dc.typeArticle
uct.catalogadorWOS
uct.indizacionSCI
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