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Artículo

Delayed Dendritic Development of Newly Generated Dentate Granule Cells by Cell-Autonomous Expression of the Amyloid Precursor Protein

Morgenstern, Nicolás AndrésIcon ; Giacomini, Damiana PaulaIcon ; Lombardi, Maria GabrielaIcon ; Castaño, Eduardo MiguelIcon ; Schinder, Alejandro FabianIcon
Fecha de publicación: 11/07/2013
Editorial: Elsevier
Revista: Molecular And Cellular Neurosciences.
ISSN: 1044-7431
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

Neuronal connectivity and synaptic remodeling are fundamental substrates for higher brain functions. Understanding their dynamics in the mammalian allocortex emerges as a critical step to tackle the cellular basis of cognitive decline that occurs during normal aging and in neurodegenerative disorders. In this work we have designed a novel approach to assess alterations in the dynamics of functional and structural connectivity elicited by chronic cell-autonomous overexpression of the human amyloid precursor protein (hAPP). We have taken advantage of the fact that the hippocampus continuously generates new dentate granule cells (GCs) to probe morphofunctional development of GCs expressing different variants of hAPP in a healthy background. hAPP was expressed together with a fluorescent reporter in neural progenitor cells of the dentate gyrus of juvenile mice by retroviral delivery. Neuronal progeny was analyzed several days post infection (dpi). Amyloidogenic cleavage products of hAPP such as the â-C terminal fragment (â-CTF) induced a substantial reduction in glutamatergic connectivity at 21 dpi, at which time new GCs undergo active growth and synaptogenesis. Interestingly, this effect was transient, since the strength of glutamatergic inputs was normal by 35 dpi. This delay in glutamatergic synaptogenesis was paralleled by a decrease in dendritic length with no changes in spine density, consistent with a protracted dendritic development without alterations in synapse formation. Finally, similar defects in newborn GC development were observed by overexpression of á-CTF, a non-amyloidogenic cleavage product of hAPP. These results indicate that hAPP can elicit protracted dendritic development independently of the amyloidogenic processing pathway.
Palabras clave: Dentate Granule Cells , Amyloid Precursor Protein , Neurogenesis
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/8359
URL: http://www.sciencedirect.com/science/article/pii/S1044743113000699
DOI: http://dx.doi.org/10.1016/j.mcn.2013.07.003
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791211/
Colecciones
Articulos(CEFYBO)
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Citación
Morgenstern, Nicolás Andrés; Giacomini, Damiana Paula; Lombardi, Maria Gabriela; Castaño, Eduardo Miguel; Schinder, Alejandro Fabian; Delayed Dendritic Development of Newly Generated Dentate Granule Cells by Cell-Autonomous Expression of the Amyloid Precursor Protein; Elsevier; Molecular And Cellular Neurosciences.; 56; 11-7-2013; 298–306
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