Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis
Date
Authors
ORTLOFF TRAUTMANN, ALEXANDER
Montserrat Guerra, Maria
Henzi, Roberto
Ortloff, Alexander
Lichtin, Nicole
Vio, Karin
Jimenez, Antonio J.
Dolores Dominguez-Pinos, Maria
Gonzalez, Cesar
Clara Jara, Maria
Hinostroza, Fernando
Rodriguez, Sara
Jara, Maryoris
Ortega, Eduardo
Guerra, Francisco
Sival, Deborah A.
den Dunnen, Wilfred F. A.
Perez-Figares, Jose M.
McAllister, James P.
Johanson, Conrad E.
Rodriguez, Esteban M.
Montserrat Guerra, Maria
Henzi, Roberto
Ortloff, Alexander
Lichtin, Nicole
Vio, Karin
Jimenez, Antonio J.
Dolores Dominguez-Pinos, Maria
Gonzalez, Cesar
Clara Jara, Maria
Hinostroza, Fernando
Rodriguez, Sara
Jara, Maryoris
Ortega, Eduardo
Guerra, Francisco
Sival, Deborah A.
den Dunnen, Wilfred F. A.
Perez-Figares, Jose M.
McAllister, James P.
Johanson, Conrad E.
Rodriguez, Esteban M.
Authors
Date
Datos de publicación:
10.1097/NEN.0000000000000203
Keywords
Cerebrospinal fluid - Congenital hydrocephalus - HTx rat - Human - Junction pathology - Neural stem cells - Neurospheres - Ventricular zone disruption
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Abstract
Fetal-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.
Description
Keywords
Cerebrospinal fluid , Congenital hydrocephalus , HTx rat , Human , Junction pathology , Neural stem cells , Neurospheres , Ventricular zone disruption
Citation
10.1097/NEN.0000000000000203