Research Papers:

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

Arianna Casciati, Katalin Dobos, Francesca Antonelli, Anett Benedek, Stefan J. Kempf, Montserrat Bellés, Andrea Balogh, Mirella Tanori, Luis Heredia, Michael J. Atkinson, Christine von Toerne, Omid Azimzadeh, Anna Saran, Geza Sáfrány, Mohammed A. Benotmane, M. Victoria Linares-Vidal, Soile Tapio, Katalin Lumniczky and Simonetta Pazzaglia _

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Oncotarget. 2016; 7:28040-28058. https://doi.org/10.18632/oncotarget.8575

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Arianna Casciati1, Katalin Dobos2, Francesca Antonelli1, Anett Benedek2, Stefan J. Kempf4,8, Montserrat Bellés3, Andrea Balogh2, Mirella Tanori1, Luis Heredia3, Michael J. Atkinson4,5, Christine von Toerne6, Omid Azimzadeh4, Anna Saran1, Geza Sáfrány2, Mohammed A. Benotmane7, M. Victoria Linares-Vidal3, Soile Tapio4, Katalin Lumniczky2, Simonetta Pazzaglia1

1Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy

2National Public Health Center - National Research Directorate for Radiobiology and Radiohygiene, Budapest, Hungary

3Physiology Unit, School of Medicine, IISPV, Rovira I Virgili University (URV), Reus, Spain

4Institute of Radiation Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Neuherberg, Germany

5Institute of Radiation Biology, Technical University Munich, Munich, Germany

6Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany

7Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Belgium

8Present address: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

Correspondence to:

Simonetta Pazzaglia, email: [email protected]

Keywords: radiation, hippocampal neurogenesis, mitochondria, proteomics, cognitive effects

Received: February 11, 2016    Accepted: March 27, 2016    Published: April 4, 2016


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.

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