Cellular Source-Specific Effects of Apolipoprotein Apo E4 on Dendrite Arborization and Dendritic Spine DevelopmentReportar como inadecuado




Cellular Source-Specific Effects of Apolipoprotein Apo E4 on Dendrite Arborization and Dendritic Spine Development - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Apolipoprotein apo E4 is the leading genetic risk factor for Alzheimer’s disease AD, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4’s cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin learning and mushroom memory spines, in the hippocampus and entorhinal cortex of 19–21-month-old female neuron-specific-enolase NSE-apoE4 and apoE4-knockin KI mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7–8 months of age. In contrast, glial fibrillary acidic protein GFAP-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.



Autor: Sachi Jain, Seo Yeon Yoon, Laura Leung, Johanna Knoferle, Yadong Huang

Fuente: http://plos.srce.hr/



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