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Cereb Cortex. 2018 Jul 1;28(7):2458-2478. doi: 10.1093/cercor/bhy096.

Hippocampal Radial Glial Subtypes and Their Neurogenic Potential in Human Fetuses and Healthy and Alzheimer's Disease Adults.

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PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Department of Pathology and Experimental Therapeutics, University of Barcelona, Bellvitge Campus, L'Hospitalet de Llobregat, Spain; Centre for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Madrid, Spain.
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
APHP, Service de Biologie du Développement, Hôpital Robert-Debré, APHP, Paris, France.
APHP, Plateforme de Bio-Pathologie et de Technologies Innovantes en Santé, Centre de Ressources Biologiques BB-0033-00064, Hôpital Lariboisière, Paris, France.
APHP, Service de Gynécologie-Obstétrique, Hôpital Lariboisère, Paris, France.
Service d'Anatomie et de Cytologie Pathologiques, Hôpital Lariboisère, Paris, France.
Department of Division of Imaging Sciences and Biomedical Engineering, Centre for the Developing Brain, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK.


Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX+ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin+ and/or GFAPδ+ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult.

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