title: Age-related effects of X-ray irradiation on mouse hippocampus.
abstract: Therapeutic irradiation of pediatric and adult patients can profoundly affect adult neurogenesis, and cognitive impairment manifests as a deficit in hippocampal-dependent functions. Age plays a major role in susceptibility to radiation, and younger children are at higher risk of cognitive decay when compared to adults. Cranial irradiation affects hippocampal neurogenesis by induction of DNA damage in neural progenitors, through the disruption of the neurogenic microenvironment, and defective integration of newborn neurons into the neuronal network. Our goal here was to assess cellular and molecular alterations induced by cranial X-ray exposure to low/moderate doses (0.1 and 2 Gy) in the hippocampus of mice irradiated at the postnatal ages of day 10 or week 10, as well as the dependency of these phenomena on age at irradiation. To this aim, changes in the cellular composition of the dentate gyrus, mitochondrial functionality, proteomic profile in the hippocampus, as well as cognitive performance were evaluated by a multidisciplinary approach. Our results suggest the induction of specific alterations in hippocampal neurogenesis, microvascular density and mitochondrial functions, depending on age at irradiation. A better understanding of how irradiation impairs hippocampal neurogenesis at low and moderate doses is crucial to minimize adverse effects of therapeutic irradiation, contributing also to radiation safety regulations.
authors.affiliation: Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Casciati
authors.affiliation: National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Dobos
authors.affiliation: Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonelli
authors.affiliation: National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: Anett
authors.initials: A
authors.lastname: Benedek
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany.|Present address: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.affiliation: Physiology Unit, School of Medicine, IISPV, Rovira I Virgili University (URV), Reus, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Bellés
authors.affiliation: National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Tanori
authors.affiliation: Physiology Unit, School of Medicine, IISPV, Rovira I Virgili University (URV), Reus, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Heredia
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany.|Institute of Radiation Biology, Technical University Munich, Munich, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: von Toerne
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.affiliation: Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.affiliation: National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: Geza
authors.initials: G
authors.lastname: Sáfrány
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Belgium.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Benotmane
authors.affiliation: Physiology Unit, School of Medicine, IISPV, Rovira I Virgili University (URV), Reus, Spain.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Linares-Vidal
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
authors.affiliation: National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Lumniczky
authors.affiliation: Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
mesh_terms: D000367:Age Factors; D000818:Animals; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000528:radiation effects*; D008297:Male; D018782:Maze Learning / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000528:radiation effects*
keywords: cognitive effects; hippocampal neurogenesis; mitochondria; proteomics; radiation