{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:06:38Z","timestamp":1785420398724,"version":"3.56.0"},"reference-count":19,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation of Singapore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81970432"],"award-info":[{"award-number":["81970432"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["81970432"],"award-info":[{"award-number":["81970432"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Prenatal exposure to ionizing radiation is a known risk factor for neurodevelopmental deficits; however, the molecular mechanisms linking chronic embryonic insult to abnormal brain development remain poorly understood. This study investigated the long-term consequences of chronic prenatal gamma irradiation throughout gestation in C57BL\/6 mice. Behavioural analysis of adult offspring revealed a specific increase in depression-like behaviours, with no significant alterations in anxiety or general exploratory activity. Immunohistochemical assessment demonstrated a significant reduction in adult hippocampal neurogenesis, marked by decreased doublecortin (DCX)-positive newborn neurons in the subgranular zone and fewer NeuN-positive mature neurons in the dentate gyrus hilus. Integrated RNA-seq, qPCR, and Western blot analyses implicated the upregulation of the Mef2c\/Egr1 signalling pathway in this neurogenic deficit. Furthermore, miRNA sequencing identified a pronounced decrease in miR-1843a-3p, which was subsequently validated to directly target Mef2c. Collectively, these findings suggest that prenatal gamma irradiation disrupts neurogenic processes and adult brain function, leading to specific behavioral abnormalities. This long-term impairment is associated with, and may be at least partially mediated by, dysregulation of the miR-1843a-3p\/Mef2c\/Egr1 pathway.<\/jats:p>","DOI":"10.3390\/cells15100912","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The miR-1843a-3p\/Mef2c\/Egr1 Axis Is Associated with Prenatal Gamma Radiation-Induced Deficits in Adult Hippocampal Neurogenesis and Behaviour"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3374-8734","authenticated-orcid":false,"given":"Yunwei","family":"Shi","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong 226001, China"},{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2447-0051","authenticated-orcid":false,"given":"Nur Salihah","family":"Lau","sequence":"additional","affiliation":[{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4863-6386","authenticated-orcid":false,"given":"Amanda Tan Ying","family":"Xin","sequence":"additional","affiliation":[{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong 226001, China"},{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-1787","authenticated-orcid":false,"given":"Feng Ru","family":"Tang","sequence":"additional","affiliation":[{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore, 16 Prince George\u2019s Park, #03-03, Singapore 118415, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, H., Ma, Z., Shen, H., Wu, Z., Liu, L., Ren, B., Wong, P., Sethi, G., and Tang, F. (2021). Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA-34a-5p\/T-Cell Intracytoplasmic Antigen-1 Pathway. Cells, 10.","DOI":"10.3390\/cells10092476"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tang, F.R., Tanaka, I.B., Wang, H., Lau, S., Tanaka, S., Tan, A., Takai, D., and Abe, A. (2024). Effects of Continuous Prenatal Low Dose Rate Irradiation on Neurobehavior, Hippocampal Cellularity, Messenger RNA and MicroRNA Expression on B6C3F1 Mice. Cells, 13.","DOI":"10.20944\/preprints202408.0050.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nrn3818","article-title":"Epigenetic and transgenerational reprogramming of brain development","volume":"16","author":"Bale","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e20059","DOI":"10.7554\/eLife.20059","article-title":"MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders","volume":"5","author":"Harrington","year":"2016","journal-title":"Elife"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0896-6273(03)00674-3","article-title":"A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval","volume":"40","author":"Bozon","year":"2003","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Duclot, F., and Kabbaj, M. (2017). The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders. Front. Behav. Neurosci., 11.","DOI":"10.3389\/fnbeh.2017.00035"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.neuro.31.060407.125631","article-title":"Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system","volume":"31","author":"Flavell","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.neuron.2018.04.001","article-title":"Different Neuronal Activity Patterns Induce Different Gene Expression Programs","volume":"98","author":"Tyssowski","year":"2018","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"595141","DOI":"10.5402\/2012\/595141","article-title":"Comparative evaluation of forced swim test and tail suspension test as models of negative symptom of schizophrenia in rodents","volume":"2012","author":"Chatterjee","year":"2012","journal-title":"ISRN Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, H., Lau, S., Tan, A., and Tang, F.R. (2024). Chronic Low-Dose-Rate Radiation-Induced Persistent DNA Damage and miRNA\/mRNA Expression Changes in Mouse Hippocampus and Blood. Cells, 13.","DOI":"10.20944\/preprints202408.2168.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1058232023","DOI":"10.1523\/JNEUROSCI.1058-23.2023","article-title":"The Mef2c Gene Dose-Dependently Controls Hippocampal Neurogenesis and the Expression of Autism-Like Behaviors","volume":"44","author":"Basu","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.1073\/pnas.0802679105","article-title":"MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function","volume":"105","author":"Barbosa","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13041-021-00892-6","article-title":"Progress on the roles of MEF2C in neuropsychiatric diseases","volume":"15","author":"Zhang","year":"2022","journal-title":"Mol. Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/ajmg.b.31071","article-title":"Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C","volume":"153b","author":"Nowakowska","year":"2010","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10048-013-0356-y","article-title":"MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways","volume":"14","author":"Paciorkowski","year":"2013","journal-title":"Neurogenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.ejmg.2016.05.017","article-title":"MEF2C haploinsufficiency syndrome: Report of a new MEF2C mutation and review","volume":"59","author":"Rocha","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0360-3016(94)90539-8","article-title":"Radiation induction of immediate early genes: Effectors of the radiation-stress response","volume":"30","author":"Weichselbaum","year":"1994","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s00066-007-1664-7","article-title":"Differential expression of egr1 and activation of microglia following irradiation in the rat brain","volume":"183","author":"Vollmann","year":"2007","journal-title":"Strahlenther. Onkol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"Ns20190147","DOI":"10.1042\/NS20190147","article-title":"MEF2C and HDAC5 regulate Egr1 and Arc genes to increase dendritic spine density and complexity in early enriched environment","volume":"4","author":"Puang","year":"2020","journal-title":"Neuronal Signal."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/912\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:25:51Z","timestamp":1779769551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":19,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cells15100912"],"URL":"https:\/\/doi.org\/10.3390\/cells15100912","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}