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Neurogenesis In The R6/2 Mouse Model Of Huntington'S Disease Is Impaired At The Level Of Neurod1

Fedele, Valentina LU ; Roybon, Laurent LU ; Nordström, Ulrika LU ; Li, Jia-Yi LU and Brundin, Patrik LU (2011) In Neuroscience 173. p.76-81
Abstract
Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several symptoms and signs of the disease (Li et al., 2005). They exhibit neurological and endocrine changes resembling some symptoms seen in humans. The reduction in neurogenesis is only apparent in the dentate gyrus as the number of newborn neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The mechanism(s) underlying the reduction in hippocampal neurogenesis is still not fully understood. Here we show that the number of neuroblasts, but not granule neuron progenitors, is greatly reduced in 11-week old transgenic mice compared with wild-type (WT) controls. We... (More)
Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several symptoms and signs of the disease (Li et al., 2005). They exhibit neurological and endocrine changes resembling some symptoms seen in humans. The reduction in neurogenesis is only apparent in the dentate gyrus as the number of newborn neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The mechanism(s) underlying the reduction in hippocampal neurogenesis is still not fully understood. Here we show that the number of neuroblasts, but not granule neuron progenitors, is greatly reduced in 11-week old transgenic mice compared with wild-type (WT) controls. We demonstrate that NeuroD1 expression is reduced in the hippocampus. This is coupled to a decreased expression of downstream markers doublecortin and calretinin in maturing neurons. Taken together, our results suggest that mutant huntingtin (Htt) causes alterations of proteins expression in hippocampal progenitors, which might contribute to cognitive deficits in Huntington's disease. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
huntingtin, hippocampus, neuroblasts, transcriptional dysregulation, transgenic mice
in
Neuroscience
volume
173
pages
76 - 81
publisher
Elsevier
external identifiers
  • wos:000286487000006
  • scopus:78650677351
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2010.08.022
language
English
LU publication?
yes
id
b6ba6f80-6526-470b-9a76-2f9945db6c73 (old id 1790685)
date added to LUP
2011-03-02 13:23:13
date last changed
2017-09-03 03:32:11
@article{b6ba6f80-6526-470b-9a76-2f9945db6c73,
  abstract     = {Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several symptoms and signs of the disease (Li et al., 2005). They exhibit neurological and endocrine changes resembling some symptoms seen in humans. The reduction in neurogenesis is only apparent in the dentate gyrus as the number of newborn neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The mechanism(s) underlying the reduction in hippocampal neurogenesis is still not fully understood. Here we show that the number of neuroblasts, but not granule neuron progenitors, is greatly reduced in 11-week old transgenic mice compared with wild-type (WT) controls. We demonstrate that NeuroD1 expression is reduced in the hippocampus. This is coupled to a decreased expression of downstream markers doublecortin and calretinin in maturing neurons. Taken together, our results suggest that mutant huntingtin (Htt) causes alterations of proteins expression in hippocampal progenitors, which might contribute to cognitive deficits in Huntington's disease. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.},
  author       = {Fedele, Valentina and Roybon, Laurent and Nordström, Ulrika and Li, Jia-Yi and Brundin, Patrik},
  issn         = {1873-7544},
  keyword      = {huntingtin,hippocampus,neuroblasts,transcriptional dysregulation,transgenic mice},
  language     = {eng},
  pages        = {76--81},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Neurogenesis In The R6/2 Mouse Model Of Huntington'S Disease Is Impaired At The Level Of Neurod1},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2010.08.022},
  volume       = {173},
  year         = {2011},
}