{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:04:29Z","timestamp":1790647469825,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The cognitive consequences of postnatal brain exposure to ionizing radiation (IR) at low to moderate doses in the adult are not fully established. Because of the advent of pediatric computed tomography scans used for head exploration, improving our knowledge of these effects represents a major scientific challenge. To evaluate how IR may affect the developing brain, models of either whole brain (WB) or targeted dorsal dentate gyrus (DDG) irradiation in C57Bl\/6J ten-day-old male mice were previously developed. Here, using these models, we assessed and compared the effect of IR (doses range: 0.25\u20132 Gy) on long-term spatial memory in adulthood using a spatial water maze task. We then evaluated the effects of IR exposure on adult hippocampal neurogenesis, a form of plasticity involved in spatial memory. Three months after WB exposure, none of the doses resulted in spatial memory impairment. In contrast, a deficit in memory retrieval was identified after DDG exposure for the dose of 1 Gy only, highlighting a non-monotonic dose-effect relationship in this model. At this dose, a brain irradiated volume effect was also observed when studying adult hippocampal neurogenesis in the two models. In particular, only DDG exposure caused alteration in cell differentiation. The most deleterious effect observed in adult hippocampal neurogenesis after targeted DDG exposure at 1 Gy may contribute to the memory retrieval deficit in this model. Altogether these results highlight the complexity of IR mechanisms in the brain that can lead or not to cognitive disorders and provide new knowledge of interest for the radiation protection of children.<\/jats:p>","DOI":"10.3390\/biology10030192","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeted Dorsal Dentate Gyrus or Whole Brain Irradiation in Juvenile Mice Differently Affects Spatial Memory and Adult Hippocampal Neurogenesis"],"prefix":"10.3390","volume":"10","author":[{"given":"C\u00e9line","family":"Serrano","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Research Department on the Biological and Health Effects of Ionizing Radiation (SESANE), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Radiobiology of Accidental Exposure (LRAcc), Research Department in Radiobiology and Regenerative Medicine (SERAMED), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Kereselidze","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Research Department on the Biological and Health Effects of Ionizing Radiation (SESANE), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louison","family":"Beugnies","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Research Department on the Biological and Health Effects of Ionizing Radiation (SESANE), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lestaevel","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Research Department on the Biological and Health Effects of Ionizing Radiation (SESANE), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8017-1322","authenticated-orcid":false,"given":"Roseline","family":"Poirier","sequence":"additional","affiliation":[{"name":"Paris-Saclay Neuroscience Institute (Neuro-PSI), University Paris-Saclay, UMR 9197 CNRS, F-91405 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Durand","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Research Department on the Biological and Health Effects of Ionizing Radiation (SESANE), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7152","DOI":"10.1200\/JCO.2005.01.214","article-title":"Intellectual and functional outcome of children 3 years old or younger who have CNS malignancies","volume":"23","author":"Fouladi","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/jpepsy\/jsl056","article-title":"Understanding the cognitive impact on children who are treated for medulloblastoma","volume":"32","author":"Palmer","year":"2007","journal-title":"J. Pediatr. Psychol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1097\/CCO.0b013e3283571a8e","article-title":"Effect of cancer therapy on neural stem cells: Implications for cognitive function","volume":"24","author":"Gibson","year":"2012","journal-title":"Curr. Opin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105371","DOI":"10.1016\/j.envint.2019.105371","article-title":"Neurodevelopmental effects of low dose ionizing radiation exposure: A systematic review of the epidemiological evidence","volume":"136","author":"Pasqual","year":"2020","journal-title":"Environ. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/rpd\/ncy184","article-title":"Organ dose estimation accounting for uncertainty for pediatric and young adult ct scans in the united kingdom","volume":"184","author":"Lee","year":"2018","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/0284185117708471","article-title":"Cognitive function following head CT in childhood: A randomized controlled follow-up trial","volume":"59","author":"Salonen","year":"2018","journal-title":"Acta Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/bmj.328.7430.19","article-title":"Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study","volume":"328","author":"Hall","year":"2004","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.3109\/0284186X.2014.899434","article-title":"No clinically relevant effect on cognitive outcomes after low-dose radiation to the infant brain: A population-based cohort study in Sweden","volume":"53","author":"Blomstrand","year":"2014","journal-title":"Acta Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1056\/NEJMra072149","article-title":"Computed tomography\u2014an increasing source of radiation exposure","volume":"357","author":"Brenner","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pearce, M.S., and Salotti, J.A. (2012). Socio-economic variation in CT scanning in Northern England, 1990\u20132002. BMC Health Serv. Res., 12.","DOI":"10.1186\/1472-6963-12-24"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"f2360","DOI":"10.1136\/bmj.f2360","article-title":"Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: Data linkage study of 11 million Australians","volume":"346","author":"Mathews","year":"2013","journal-title":"BMJ"},{"key":"ref_12","first-page":"721","article-title":"Computed Tomography in Germany","volume":"113","author":"Pokora","year":"2016","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/09553009214552031","article-title":"Prenatal irradiation and spatial memory in mice: Investigation of critical period","volume":"62","author":"Sienkiewicz","year":"1992","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuro.2014.09.002","article-title":"Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice","volume":"45","author":"Buratovic","year":"2014","journal-title":"Neurotoxicology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1750-1326-9-57","article-title":"The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation","volume":"9","author":"Kempf","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbr.2016.02.008","article-title":"Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose--response effects and strain and sex comparison","volume":"304","author":"Eriksson","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17262","DOI":"10.1038\/s41598-018-35579-x","article-title":"Development of whole brain versus targeted dentate gyrus irradiation model to explain low to moderate doses of exposure effects in mice","volume":"8","author":"Kereselidze","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28040","DOI":"10.18632\/oncotarget.8575","article-title":"Age-related effects of X-ray irradiation on mouse hippocampus","volume":"7","author":"Casciati","year":"2016","journal-title":"Oncotarget"},{"key":"ref_19","unstructured":"(2020, December 30). Strategic Research Agenda of the Multidisciplinary European Low Dose Initiative (MELODI)\u20142019. Available online: http:\/\/www.melodi-online.eu\/doc\/MELODI%20SRA%202019%20%20post-consultation%20draft%20FINAL2.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrn3785","article-title":"Functional organization of the hippocampal longitudinal axis","volume":"15","author":"Strange","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.ijrobp.2009.06.025","article-title":"Factors influencing neurocognitive outcomes in young patients with benign and low-grade brain tumors treated with stereotactic conformal radiotherapy","volume":"77","author":"Jalali","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1093\/neuonc\/noq104","article-title":"Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies","volume":"12","author":"Armstrong","year":"2010","journal-title":"Neuro Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/neuonc\/nos120","article-title":"Estimated clinical benefit of protecting, in the developing brain during radiation therapy for pediatric medulloblastoma","volume":"14","author":"Blomstrand","year":"2012","journal-title":"Neuro Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1093\/neuonc\/nos303","article-title":"Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: A prospective study","volume":"15","author":"Redmond","year":"2013","journal-title":"Neuro Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a018812","DOI":"10.1101\/cshperspect.a018812","article-title":"Neurogenesis in the Adult Hippocampus","volume":"7","author":"Kempermann","year":"2015","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2016.10.021","article-title":"Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior","volume":"167","author":"Schafer","year":"2016","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"a019026","DOI":"10.1101\/cshperspect.a019026","article-title":"Adult Neurogenesis and Psychiatric Disorders","volume":"8","author":"Kang","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainres.2016.05.015","article-title":"Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory","volume":"1644","author":"Lieberwirth","year":"2016","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00726-013-1489-x","article-title":"Functional implications of hippocampal adult neurogenesis in intellectual disabilities","volume":"45","year":"2013","journal-title":"Amino Acids"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Semple, B.D., Blomgren, K., Gimlin, K., Ferriero, D.M., and Noble-Haeusslein, L.J. (2013). Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Prog. Neurobiol., 1\u201316.","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0006-8993(99)02231-3","article-title":"Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice","volume":"853","author":"Eriksson","year":"2000","journal-title":"Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5919","DOI":"10.1073\/pnas.0811054106","article-title":"Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory","volume":"106","author":"Trouche","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1073\/pnas.1220558110","article-title":"Zif268\/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning","volume":"110","author":"Veyrac","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1093\/hmg\/ddz296","article-title":"The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis","volume":"29","author":"Castillon","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/09553000310001610998","article-title":"IL-1\u03b2, TNF\u03b1 and IL-6 induction in the rat brain after partial-body irradiation: Role of vagal afferents","volume":"79","author":"Marquette","year":"2003","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_36","first-page":"248","article-title":"Early cognitive changes due to whole body gamma-irradiation: A behavioral and diffusion tensor imaging study in mice","volume":"8","author":"Kumar","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1748-717X-9-139","article-title":"Why and how to spare the hippocampus during brain radiotherapy: The developing role of hippocampal avoidance in cranial radiotherapy","volume":"9","author":"Kazda","year":"2014","journal-title":"Radiat. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.bbi.2011.09.012","article-title":"Adult murine hippocampal neurogenesis is inhibited by sustained IL-1\u03b2 and not rescued by voluntary running","volume":"2","author":"Wu","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9764","DOI":"10.1523\/JNEUROSCI.4790-14.2015","article-title":"miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction","volume":"35","author":"Woodbury","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/nm749","article-title":"Irradiation induces neural precursor-cell dysfunction","volume":"8","author":"Monje","year":"2002","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1088417","article-title":"Inflammatory Blockade Restores Adult Hippocampal Neurogenesis","volume":"302","author":"Monje","year":"2003","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"S\u00e1ndor, N., and Walter, F.R. (2014). Low Dose Cranial Irradiation-Induced Cerebrovascular Damage Is Reversible in Mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112397"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.neuroscience.2010.09.047","article-title":"Young hippocampal neurons are critical for recent and remote spatial memory in adult mice","volume":"171","author":"Goodman","year":"2010","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nbd.2018.04.007","article-title":"Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome","volume":"115","author":"Castillon","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fnsys.2013.00074","article-title":"The mechanisms for pattern completion and pattern separation in the hippocampus","volume":"7","author":"Rolls","year":"2013","journal-title":"Front. Syst. Neurosci."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/3\/192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:27Z","timestamp":1760160747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/3\/192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biology10030192"],"URL":"https:\/\/doi.org\/10.3390\/biology10030192","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]}}}