Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice

Neurobiol Dis. 2005 Dec;20(3):744-51. doi: 10.1016/j.nbd.2005.05.006. Epub 2005 Jun 13.

Abstract

We investigated whether cell proliferation and neurogenesis are altered in R6/2 transgenic Huntington's disease mice. Using bromodeoxyuridine (BrdU), we found a progressive decrease in the number of proliferating cells in the dentate gyrus of R6/2 mice. This reduction was detected in pre-symptomatic mice, and by 11.5 weeks, R6/2 mice had 66% fewer newly born cells in the hippocampus. The results were confirmed by immunohistochemistry for the cell cycle markers Ki-67 and proliferating cell nuclear antigen (PCNA). We did not observe changes in cell proliferation in the R6/2 subventricular zone, indicating that the decrease in cell proliferation is specific for the hippocampus. This decrease corresponded to a reduction in actual hippocampal neurogenesis as assessed by double immunostaining for BrdU and the neuronal marker neuronal nuclei (NeuN) and by immunohistochemistry for the neuroblast marker doublecortin. Reduced hippocampal neurogenesis may be a novel neuropathological feature in R6/2 mice that could be assessed when evaluating potential therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Bromodeoxyuridine
  • Cell Division / genetics
  • Cell Proliferation*
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Female
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / physiopathology
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / genetics
  • Neurons / metabolism*
  • Neurons / pathology
  • Neuropeptides / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Stem Cells / metabolism

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • HTT protein, human
  • Huntingtin Protein
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Neuropeptides
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • doublecortin protein
  • Bromodeoxyuridine