Age-related effects of X-ray irradiation on mouse hippocampus

// Arianna Casciati 1 , Katalin Dobos 2 , Francesca Antonelli 1 , Anett Benedek 2 , Stefan J. Kempf 4, 8 , Montserrat Bellés 3 , Andrea Balogh 2 , Mirella Tanori 1 , Luis Heredia 3 , Michael J. Atkinson 4, 5 , Christine von Toerne 6 , Omid Azimzadeh 4 , Anna Saran 1 , Geza Sáfrány 2 , Mohammed A. Benotmane 7 , M. Victoria Linares-Vidal 3 , Soile Tapio 4 , Katalin Lumniczky 2 , Simonetta Pazzaglia 1 1 Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy 2 National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary 3 Physiology Unit, School of Medicine, IISPV, Rovira I Virgili University (URV), Reus, Spain 4 Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany 5 Institute of Radiation Biology, Technical University Munich, Munich, Germany 6 Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany 7 Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Belgium 8 Present address: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark Correspondence to: Simonetta Pazzaglia, email: simonetta.pazzaglia@enea.it Keywords: radiation, hippocampal neurogenesis, mitochondria, proteomics, cognitive effects Received: February 11, 2016 Accepted: March 27, 2016 Published: April 4, 2016 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.