title: Reduction of the immunostainable length of the hippocampal dentate granule cells' primary cilia in 3xAD-transgenic mice producing human Aβ(1-42) and tau.
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.
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, ON, Canada. Balu.Chakravarthy@nrc-cnrc.gc.ca
authors.forename: Balu
authors.initials: B
authors.lastname: Chakravarthy
authors.forename: Chantal
authors.initials: C
authors.lastname: Gaudet
authors.forename: Michel
authors.initials: M
authors.lastname: Ménard
authors.forename: Leslie
authors.initials: L
authors.lastname: Brown
authors.forename: Trevor
authors.initials: T
authors.lastname: Atkinson
authors.forename: Frank M
authors.initials: FM
authors.lastname: Laferla
authors.forename: Shingo
authors.initials: S
authors.lastname: Ito
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
authors.forename: James
authors.initials: J
authors.lastname: Whitfield
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013194:Staining and Labeling; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D017475:Receptors, Nerve Growth Factor; D017481:Receptors, Somatostatin; C517634:Ngfr protein, mouse; C075222:amyloid beta-protein (1-42); C103631:somatostatin receptor 3; D016875:tau Proteins