title: Vulnerability of calbindin, calretinin and parvalbumin in a transgenic/knock-in APPswe/PS1dE9 mouse model of Alzheimer disease together with disruption of hippocampal neurogenesis.
abstract: The pathogenesis of Alzheimer disease (AD) is characterized by accumulation of β-amyloid protein in the brain (in both soluble and insoluble forms) and by the presence of intracellular neurofibrillary tangles (NFTs), leading to neurotoxicity. The exact mechanisms whereby Aβ triggers brain alterations are unclear. However, accumulating evidence suggests that a deregulation of Ca(2+) signaling may play a major role in disease progression. Calcium-buffering proteins, including calbindin-D28K (CB), calretinin (CR) and parvalbumin (PV), may offer neuroprotection by maintaining calcium homeostasis. Although marked reductions in these proteins have been observed in the brains of mice and humans with AD, their contribution to AD pathology remains unclear. The aim of the present study was to analyze distribution patterns of CB(+,) CR(+) and PV(+) interneurons in different areas of the hippocampus, a brain region that is severely affected in AD. A transgenic knock-in APPswe/PS1dE9 mouse model of familial AD was used. The data were obtained from the brains of 3- and 12-month-old animals. These ages roughly correspond to an early mature adult (prior to clinical manifestations) and a late middle-age (clinical symptoms readily detectable) phase in human AD patients. Immunostaining revealed increases in CB and PV immunoreactivity (IR) in the hippocampus of 3-month-old transgenic mice, compared to wild-type animals. Possibly, these proteins are upregulated in an attempt to control cellular homeostasis and synaptic plasticity. However, the pattern of CB-IR was reversed in 12-month-old animals, potentially indicating a loss of cellular capacity to respond to pathophysiological processes. In addition, at this age, a noticeable increase in PV-IR was observed, suggesting the presence of hippocampal network hyperactivity in older AD-like mice. Our results indicate that CaBP(+) neuronal subpopulations play a role in adult neurogenesis and in AD pathology, particularly at early disease stages, suggesting that these neurons may serve as potential predictors of future AD in non-demented individuals.
authors.affiliation: Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, 08028 Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Verdaguer
authors.affiliation: Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, 08028 Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Brox
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, C/Joan XXIII, s/n, 08028 Barcelona, Spain.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Petrov
authors.affiliation: Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, 5 Poniente N° 1670, 3460000 Talca, Chile.
authors.forename: Jordi
authors.initials: J
authors.lastname: Olloquequi
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, 08028 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, C/Joan XXIII, s/n, 08028 Barcelona, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: de Lemos
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, C/Joan XXIII, s/n, 08028 Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.affiliation: Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, 08028 Barcelona, Spain. Electronic address: cauladell@ub.edu.
authors.forename: Carme
authors.initials: C
authors.lastname: Auladell
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism*; D064026:Calbindins / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009431:Neural Conduction / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism*
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins
keywords: APPswe/PS1dE9 mouse; Alzheimer disease; Calbindin; Calretinin; Hippocampus; Parvalbumin