Temporal Dynamics of Hippocampal Neurogenesis in Chronic Neurodegeneration

Overview

Journal Brain

Publisher Oxford University Press

Specialty Neurology

Date 2014 Jun 20

PMID 24941947

Citations 42

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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