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A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse

A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse
A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse
Neural stem and progenitor cells are located in the subependyma of the adult forebrain. An increase in adult subependymal cell proliferation is reported after various kinds of brain injury. We demonstrate an expansion of neural precursor cells in the postnatal subependyma in a murine genetic disease model of Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay as an index of the number of neural stem cells in vivo and to assess proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess the progenitor cell population and their fates. Disease progression in this model leads to an increase in the numbers of neural stem cells in the adult striatal subependyma. This increase is produced cell non-autonomously by events in the R6/2 brains as the mice become increasingly symptomatic. Once the neural stem cell increase is induced in vivo, it is maintained during in vitro passaging of neural stem cells, but the neural stem cell increase is not reproduced during in vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition, we show that some of the R6/2 neural progenitor cells show a change from their normal migration destiny toward the olfactory bulb. Instead, some of these cells migrate into the striatum, one of the main affected areas in HD. Our findings demonstrate that HD damage recruits precursor cells in two ways: expansion of neural stem cells and altered migration of progenitor cells.
neural stem cells, progenitor cells, huntington's disease, subependyma, migration, R/2 mice
10452-10460
Batista, C.M.C.
6e7ab9de-842b-44cf-b677-6a6b73ab7ec6
Kippin, T.E.
89121494-63f7-401a-a5f8-a810e35953fe
Willaime-Morawek, S.
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Shimabukuro, M.K.
49ff3fab-a5b8-42bd-b13b-0ad25f9f87ce
Akamatsu, W.
f65b526f-cb72-4464-bfda-59b82a1e248e
van der Kooy, D.
b9a759b8-56ec-4059-9421-02337257fa16
Batista, C.M.C.
6e7ab9de-842b-44cf-b677-6a6b73ab7ec6
Kippin, T.E.
89121494-63f7-401a-a5f8-a810e35953fe
Willaime-Morawek, S.
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Shimabukuro, M.K.
49ff3fab-a5b8-42bd-b13b-0ad25f9f87ce
Akamatsu, W.
f65b526f-cb72-4464-bfda-59b82a1e248e
van der Kooy, D.
b9a759b8-56ec-4059-9421-02337257fa16

Batista, C.M.C., Kippin, T.E., Willaime-Morawek, S., Shimabukuro, M.K., Akamatsu, W. and van der Kooy, D. (2006) A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse. Journal of Neuroscience, 26 (41), 10452-10460. (doi:10.1523/JNEUROSCI.2850-06.2006). (PMID:17035529)

Record type: Article

Abstract

Neural stem and progenitor cells are located in the subependyma of the adult forebrain. An increase in adult subependymal cell proliferation is reported after various kinds of brain injury. We demonstrate an expansion of neural precursor cells in the postnatal subependyma in a murine genetic disease model of Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay as an index of the number of neural stem cells in vivo and to assess proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess the progenitor cell population and their fates. Disease progression in this model leads to an increase in the numbers of neural stem cells in the adult striatal subependyma. This increase is produced cell non-autonomously by events in the R6/2 brains as the mice become increasingly symptomatic. Once the neural stem cell increase is induced in vivo, it is maintained during in vitro passaging of neural stem cells, but the neural stem cell increase is not reproduced during in vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition, we show that some of the R6/2 neural progenitor cells show a change from their normal migration destiny toward the olfactory bulb. Instead, some of these cells migrate into the striatum, one of the main affected areas in HD. Our findings demonstrate that HD damage recruits precursor cells in two ways: expansion of neural stem cells and altered migration of progenitor cells.

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More information

Published date: 11 October 2006
Keywords: neural stem cells, progenitor cells, huntington's disease, subependyma, migration, R/2 mice

Identifiers

Local EPrints ID: 48492
URI: http://eprints.soton.ac.uk/id/eprint/48492
PURE UUID: 8f4d5780-8d05-4126-8dd1-807fab03ccb3
ORCID for S. Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

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Date deposited: 26 Sep 2007
Last modified: 03 Dec 2019 01:44

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