{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:30:23Z","timestamp":1793424623608,"version":"4.5.0"},"reference-count":40,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,3,8]]},"abstract":"<jats:p>Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), \u03b2-tubulin and dendritic spines were decreased. In the irradiated neurons, the \u03b2-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF\/TrkB signaling pathway may not be involved in this process.<\/jats:p>","DOI":"10.1667\/rade-23-00168.1","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T04:40:19Z","timestamp":1705552819000},"page":"240-251","source":"Crossref","is-referenced-by-count":4,"title":["TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF\/TrkB Pathway"],"prefix":"10.1667","volume":"201","author":[{"given":"Rui","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedi","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Oncology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Oncology Radiotherapy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"10","doi-asserted-by":"crossref","unstructured":"VK Parihar  and CL Limoli  \"Proc Natl Acad Sci U S A.\"  110, \"Cranial irradiation compromises neuronal architecture in the hippocampus.\" 12822 (2013)","DOI":"10.1073\/pnas.1307301110"},{"key":"11","doi-asserted-by":"crossref","unstructured":"SH Ou, F Wu, D Harrich, et al.  \"J Virol.\"  69, \"Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs.\" 3584 (1995)","DOI":"10.1128\/jvi.69.6.3584-3596.1995"},{"key":"1","doi-asserted-by":"crossref","unstructured":"DW Andrews, CB Scott, PW Sperduto, et al.  \"Lancet.\"  22, \"Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.\" 1665 (2004)","DOI":"10.1016\/S0140-6736(04)16250-8"},{"key":"2","doi-asserted-by":"crossref","unstructured":"Y Hirano, K Konishi, Y Ejima,  \"Int J Clin Oncol.\"  25, \"Utility of whole brain radiation therapy for leptomeningeal carcinomatosis.\" 1432 (2020)","DOI":"10.1007\/s10147-020-01668-z"},{"key":"3","doi-asserted-by":"crossref","unstructured":"S Saad  and TJ Wang  \"Am J Clin Oncol.\"  38, \"Neurocognitive Deficits After Radiation Therapy for Brain Malignancies.\" 634 (2015)","DOI":"10.1097\/COC.0000000000000158"},{"key":"4","doi-asserted-by":"crossref","unstructured":"FE Froklage, LJ Oosterbaan, EM Sizoo, et al.  \"J Neurooncol.\"  116, \"Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study.\" 387 (2014)","DOI":"10.1007\/s11060-013-1310-4"},{"key":"5","doi-asserted-by":"crossref","unstructured":"DR Grosshans, CA Meyers, PK Allen, et al.  \"Cancer.\"  112, \"Neurocognitive function in patients with small cell lung cancer: effect of prophylactic cranial irradiation.\" 589 (2008)","DOI":"10.1002\/cncr.23222"},{"key":"6","doi-asserted-by":"crossref","unstructured":"A Sun, K Bae, EM Gore, et al.  \"J Clin Oncol.\"  29, \"Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis.\" 279 (2011)","DOI":"10.1200\/JCO.2010.29.6053"},{"key":"7","doi-asserted-by":"crossref","unstructured":"J Raber, AR Allen, S Weber, et al.  \"Behav Brain Res.\"  302, \"Effect of behavioral testing on spine density of basal dendrites in the CA1 region of the hippocampus modulated by (56)Fe irradiation.\" 263 (2016)","DOI":"10.1016\/j.bbr.2016.01.035"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Y Son, M Yang, H Wang, et al.  \"Brain Behavior & Immunity.\"  45, \"Hippocampal dysfunctions caused by cranial irradiation: A review of the experimental evidence.\" 287 (2015)","DOI":"10.1016\/j.bbi.2015.01.007"},{"key":"9","doi-asserted-by":"crossref","unstructured":"SJ Kempf, S Sepe, C von Toerne, et al.  \"J Proteome Res.\"  14, \"Neonatal Irradiation Leads to Persistent Proteome Alterations Involved in Synaptic Plasticity in the Mouse Hippocampus and Cortex.\" 4674 (2015)","DOI":"10.1021\/acs.jproteome.5b00564"},{"key":"12","doi-asserted-by":"crossref","unstructured":"F Chiti  and CM Dobson  \"Annu Rev Biochem.\"  75, \"Protein misfolding, functional amyloid, and human disease.\" 333 (2006)","DOI":"10.1146\/annurev.biochem.75.101304.123901"},{"key":"13","doi-asserted-by":"crossref","unstructured":"YZ Liao, J Ma, JZ Dou,  \"Mol Neurobiol.\"  \"The Role of TDP-43 in Neurodegenerative Disease.\" (2022)","DOI":"10.1007\/s12035-022-02847-x"},{"key":"14","doi-asserted-by":"crossref","unstructured":"N Aoki, ME Murray, K Ogaki, et al.  \"Acta Neuropathol.\"  129, \"Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A.\" 53 (2015)","DOI":"10.1007\/s00401-014-1358-z"},{"key":"15","doi-asserted-by":"crossref","unstructured":"Q Zhang, X Li, R He, et al.  \"Brain Res.\"  1681, \"The effect of brain-derived neurotrophic factor on radiation-induced neuron architecture impairment is associated with the NFATc4\/3 pathway.\" 21 (2018)","DOI":"10.1016\/j.brainres.2017.12.032"},{"key":"16","doi-asserted-by":"crossref","unstructured":"R Sun, LY Zhang, LS Chen, et al.  \"Neurol Res.\"  38, \"Long-term outcome of changes in cognitive function of young rats after various\/different doses of whole brain irradiation.\" 647 (2016)","DOI":"10.1080\/01616412.2016.1188483"},{"key":"17","doi-asserted-by":"crossref","unstructured":"M Hasegawa, T Arai, T Nonaka, et al.  \"Ann Neurol.\"  64, \"Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.\" 60 (2008)","DOI":"10.1002\/ana.21425"},{"key":"19","doi-asserted-by":"crossref","unstructured":"LA Mongiat  and AF Schinder  \"Eur J Neurosci.\"  33, \"Adult neurogenesis and the plasticity of the dentate gyrus network.\" 1055 (2011)","DOI":"10.1111\/j.1460-9568.2011.07603.x"},{"key":"20","doi-asserted-by":"crossref","unstructured":"W Deng, JB Aimone, FH Gage,  \"Nat Rev Neurosci.\"  11, \"New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?\" 339 (2010)","DOI":"10.1038\/nrn2822"},{"key":"21","doi-asserted-by":"crossref","unstructured":"JB Aimone, W Deng, FH Gage,  \"Neuron.\"  70, \"Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation.\" 589 (2011)","DOI":"10.1016\/j.neuron.2011.05.010"},{"key":"22","doi-asserted-by":"crossref","unstructured":"F Gao, M Hu, J Zhang, et al.  \"Acta Neuropathol.\"  144, \"TDP-43 drives synaptic and cognitive deterioration following traumatic brain injury.\" 187 (2022)","DOI":"10.1007\/s00401-022-02449-w"},{"key":"23","doi-asserted-by":"crossref","unstructured":"J Ni, Y Ren, T Su, et al.  \"Mol Psychiatry.\"  \"Loss of TDP-43 function underlies hippocampal and cortical synaptic deficits in TDP-43 proteinopathies.\" (2021)","DOI":"10.1038\/s41380-021-01346-0"},{"key":"24","doi-asserted-by":"crossref","unstructured":"M Neumann, LK Kwong, EB Lee, et al.  \"Acta Neuropathol.\"  117, \"Phosphorylation of S409\/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies.\" 137 (2009)","DOI":"10.1007\/s00401-008-0477-9"},{"key":"25","doi-asserted-by":"crossref","unstructured":"D Zhang, W Zhou, TT Lam, et al.  \"Neuro Oncol.\"  20, \"Radiation induces age-dependent deficits in cortical synaptic plasticity.\" 1207 (2018)","DOI":"10.1093\/neuonc\/noy052"},{"key":"26","doi-asserted-by":"crossref","unstructured":"SJ Kempf, S Buratovic, C von Toerne, et al.  \"PLoS One.\"  9, \"Ionising radiation immediately impairs synaptic plasticity-associated cytoskeletal signalling pathways in HT22 cells and in mouse brain: an in vitro\/in vivo comparison study.\" e110464 (2014)","DOI":"10.1371\/journal.pone.0110464"},{"key":"27","doi-asserted-by":"crossref","unstructured":"M Bykhovskaia,  \"Semin Cell Dev Biol.\"  22, \"Synapsin regulation of vesicle organization and functional pools.\" 387 (2011)","DOI":"10.1016\/j.semcdb.2011.07.003"},{"key":"28","doi-asserted-by":"crossref","unstructured":"LI Benowitz  and A Routtenberg  \"Trends Neurosci.\"  20, \"GAP-43: an intrinsic determinant of neuronal development and plasticity.\" 84 (1997)","DOI":"10.1016\/S0166-2236(96)10072-2"},{"key":"29","doi-asserted-by":"crossref","unstructured":"PC Bressloff  and BA Earnshaw  \"Biophys J.\"  96, \"A dynamic corral model of receptor trafficking at a synapse.\" 1786 (2009)","DOI":"10.1016\/j.bpj.2008.12.3889"},{"key":"30","doi-asserted-by":"crossref","unstructured":"M Song, K Martinowich, FS Lee,  \"Mol Psychiatry.\"  22, \"BDNF at the synapse: why location matters.\" 1370 (2017)","DOI":"10.1038\/mp.2017.144"},{"key":"31","doi-asserted-by":"crossref","unstructured":"E Palasz, A Wysocka, A Gasiorowska, et al.  \"Int J Mol Sci.\"  \"BDNF as a Promising Therapeutic Agent in Parkinson's Disease.\" 21 (2020)","DOI":"10.3390\/ijms21031170"},{"key":"32","doi-asserted-by":"crossref","unstructured":"JY Tann, LW Wong, S Sajikumar, et al.  \"Embo j.\"  38, \"Abnormal TDP-43 function impairs activity-dependent BDNF secretion, synaptic plasticity, and cognitive behavior through altered Sortilin splicing.\" (2019)","DOI":"10.15252\/embj.2018100989"},{"key":"33","doi-asserted-by":"crossref","unstructured":"B Hing, L Sathyaputri, JB Potash,  \"Am J Med Genet B Neuropsychiatr Genet.\"  177, \"A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder.\" 143 (2018)","DOI":"10.1002\/ajmg.b.32616"},{"key":"34","doi-asserted-by":"crossref","unstructured":"SN Zarneshan, S Fakhri, H Khan,  \"Pharmacol Res.\"  177, \"Targeting Akt\/CREB\/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach.\" 106099 (2022)","DOI":"10.1016\/j.phrs.2022.106099"},{"key":"35","doi-asserted-by":"crossref","unstructured":"JF Ji, SJ Ji, R Sun, et al.  \"Biochem Biophys Res Com-mun.\"  443, \"Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway.\" 646 (2014)","DOI":"10.1016\/j.bbrc.2013.12.031"},{"key":"36","doi-asserted-by":"crossref","unstructured":"JJ Herzog, W Xu, M Deshpande, et al.  \"Proc Natl Acad Sci U S A.\"  117, \"TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression.\" 11760 (2020)","DOI":"10.1073\/pnas.1917038117"},{"key":"37","doi-asserted-by":"crossref","unstructured":"M Sekiguchi  and N Matsushita  \"Int J Mol Sci.\"  \"DNA Damage Response Regulation by Histone Ubiquitination.\" 23","DOI":"10.3390\/ijms23158187"},{"key":"38","doi-asserted-by":"crossref","unstructured":"J Mitra, EN Guerrero, PM Hegde, et al.  \"Proc Natl Acad Sci U S A.\"  116, \"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects.\" 4696 (2019)","DOI":"10.1073\/pnas.1818415116"},{"key":"39","doi-asserted-by":"crossref","unstructured":"A Konopka, DR Whelan, MS Jamali, et al.  \"Mol Neurodegener.\"  15, \"Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations.\" 51","DOI":"10.1186\/s13024-020-00386-4"},{"key":"40","doi-asserted-by":"crossref","unstructured":"LY Zhang, LS Chen, R Sun, et al.  \"J Radiat Res.\"  54, \"Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment.\" 235 (2013)","DOI":"10.1093\/jrr\/rrs095"},{"key":"18","doi-asserted-by":"crossref","unstructured":"S Ji, Y Tian, Y Lu, et al.  \"Brain Res.\"  1577, \"Irradiation-induced hippocampal neurogenesis impairment is associated with epigenetic regulation of bdnf gene transcription.\" 77 (2014)","DOI":"10.1016\/j.brainres.2014.06.035"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00168.1\/3318479\/10.1667_rade-23-00168.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00168.1\/3318479\/10.1667_rade-23-00168.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:33:22Z","timestamp":1793421202000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-201\/issue-3\/RADE-23-00168.1\/TDP-43-was-Involved-in-Radiation-induced-Neuronal-Damage-and\/10.1667\/RADE-23-00168.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,8]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-23-00168.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,8]]}}}