Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1

V. Fedele, L. Roybon, U. Nordström, J. Y. Li, P. Brundin

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)76-81
Number of pages6
JournalNeuroscience
Volume173
DOIs
Publication statusPublished - Jan 26 2011

Fingerprint

Huntington Disease
Neurogenesis
Transgenic Mice
Neurons
Hippocampus
Calbindin 2
Lateral Ventricles
Olfactory Bulb
Dentate Gyrus
Signs and Symptoms
Phenotype
Proteins

Keywords

  • Hippocampus
  • Huntingtin
  • Neuroblasts
  • Transcriptional dysregulation
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1. / Fedele, V.; Roybon, L.; Nordström, U.; Li, J. Y.; Brundin, P.

In: Neuroscience, Vol. 173, 26.01.2011, p. 76-81.

Research output: Contribution to journalArticle

Fedele, V. ; Roybon, L. ; Nordström, U. ; Li, J. Y. ; Brundin, P. / Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1. In: Neuroscience. 2011 ; Vol. 173. pp. 76-81.
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