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Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration

Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration
Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration
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 ?-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
0006-8950
1-17
Gómez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Suzzi, Stefano
4cca50b7-4132-4528-8c59-2102e269cbeb
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Fransen, Nina L.
767c840d-b5d7-4130-b8e5-af2aa4d292e7
Al-Malki, Hussain
f4f2db11-ed59-48dc-9ce5-b32eab9e1733
Cebrian-silla, A.
8880c664-d787-4325-9ba8-3864b7418aca
García-verdugo, Jm
054230b3-e4ad-4801-b42c-8c7b6287d1a5
Riecken, K.
386307f1-46f2-4774-8d0a-40df7e0fe7d5
Fehse, B.
42f61f07-238b-4441-89be-aef92d350fef
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gómez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Suzzi, Stefano
4cca50b7-4132-4528-8c59-2102e269cbeb
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Fransen, Nina L.
767c840d-b5d7-4130-b8e5-af2aa4d292e7
Al-Malki, Hussain
f4f2db11-ed59-48dc-9ce5-b32eab9e1733
Cebrian-silla, A.
8880c664-d787-4325-9ba8-3864b7418aca
García-verdugo, Jm
054230b3-e4ad-4801-b42c-8c7b6287d1a5
Riecken, K.
386307f1-46f2-4774-8d0a-40df7e0fe7d5
Fehse, B.
42f61f07-238b-4441-89be-aef92d350fef
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4

Gómez-Nicola, Diego, Suzzi, Stefano, Vargas-Caballero, Mariana, Fransen, Nina L., Al-Malki, Hussain, Cebrian-silla, A., García-verdugo, Jm, Riecken, K., Fehse, B. and Perry, V. Hugh (2014) Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration. Brain, 1-17. (doi:10.1093/brain/awu155). (PMID:24941947)

Record type: Article

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 ?-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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Accepted/In Press date: 25 April 2014
Published date: 18 June 2014
Keywords: neural stem cells, adult neurogenesis, alzheimer’s disease, variant CJD
Organisations: Biomedicine

Identifiers

Local EPrints ID: 366040
URI: https://eprints.soton.ac.uk/id/eprint/366040
ISSN: 0006-8950
PURE UUID: ea81639d-6e9e-4268-a208-78e02ae7d39f
ORCID for Diego Gómez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001

Catalogue record

Date deposited: 24 Jun 2014 15:24
Last modified: 06 Jun 2018 12:33

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