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Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration

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Diego Gomez-Nicola, Stefano Suzzi, Mariana Vargas-Caballero, Nina L. Fransen, Hussain Al-Malki, Arantxa Cebrian-Silla, Jose Manuel Garcia-Verdugo, Kristoffer Riecken, Boris Fehse, V. Hugh Perry
DOI: http://dx.doi.org/10.1093/brain/awu155 2312-2328 First published online: 18 June 2014

Summary

The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer’s disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases.

  • neural stem cells
  • adult neurogenesis
  • Alzheimer’s disease
  • variant CJD
  • Abbreviations
    BrdU
    5-bromo-2'-deoxyuridine
    CJD
    Creutzfeldt-Jakob’s disease
    EdU
    5-ethynyl-2'-deoxyuridine
    PrP
    prion protein
  • This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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