Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human Aβ(1-42) and tau

Biochem Biophys Res Commun. 2012 Oct 12;427(1):218-22. doi: 10.1016/j.bbrc.2012.09.056. Epub 2012 Sep 17.

Abstract

The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75(NTR)). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both Aβ(1-42) and the mutant human tau protein tau(P301L,) the dentate granule cells still had immunostainable SSTR3- and p75(NTR)-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of Aβ(1-42) or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of Aβ(1-42) and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Animals
  • Biomarkers / metabolism
  • Cilia / metabolism
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / biosynthesis*
  • Peptide Fragments / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Somatostatin / metabolism
  • Staining and Labeling
  • tau Proteins / biosynthesis*
  • tau Proteins / genetics

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • Receptors, Nerve Growth Factor
  • Receptors, Somatostatin
  • Ngfr protein, mouse
  • amyloid beta-protein (1-42)
  • somatostatin receptor 3
  • tau Proteins