title: Increased Calcium-Sensing Receptor Immunoreactivity in the Hippocampus of a Triple Transgenic Mouse Model of Alzheimer's Disease.
abstract: The Calcium-Sensing Receptor (CaSR) is a G-protein coupled, 7-transmembrane domain receptor ubiquitously expressed throughout the body, brain including. The role of CaSR in the CNS is not well understood; its expression is increasing during development, which has been implicated in memory formation and consolidation, and CaSR localization in nerve terminals has been related to synaptic plasticity and neurotransmission. There is an emerging evidence of CaSR involvement in neurodegenerative disorders and Alzheimer's disease (AD) in particular, where the over-production of β-amyloid peptides was reported to activate CaSR. In the present study, we performed CaSR immunohistochemical and densitometry analysis in the triple transgenic mouse model of AD (3xTg-AD). We found an increase in the expression of CaSR in hippocampal CA1 area and in dentate gyrus in the 3xTg-AD mice when compared to non-transgenic control animals. This increase was significant at 9 months of age and further increased at 12 and 18 months of age. This increase paralleled the accumulation of β-amyloid plaques with age. Increased expression of CaSR favors β-amyloidogenic pathway following direct interactions between β-amyloid and CaSR and hence may contribute to the pathological evolution of the AD. In the framework of this paradigm CaSR may represent a novel therapeutic target.
authors.affiliation: Human Histology and Embryology Unit, Medical School, University of VeronaVerona, Italy; Basque Foundation for Science, Achúcarro Basque Center for Neuroscience, IKERBASQUEBilbao, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU)Leioa, Spain.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gardenal
authors.affiliation: Human Histology and Embryology Unit, Medical School, University of Verona Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarini
authors.affiliation: Human Histology and Embryology Unit, Medical School, University of Verona Verona, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
authors.affiliation: Human Histology and Embryology Unit, Medical School, University of Verona Verona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
authors.affiliation: Basque Foundation for Science, Achúcarro Basque Center for Neuroscience, IKERBASQUEBilbao, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU)Leioa, Spain; Faculty of Biology, Medicine and Health, The University of ManchesterManchester, UK.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.affiliation: Basque Foundation for Science, Achúcarro Basque Center for Neuroscience, IKERBASQUEBilbao, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU)Leioa, Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Rodríguez
keywords: Alzheimer's disease; calcium sensing receptor (CaSR); hippocampus; tau; β-amyloid